Dermatological peptide drug conjugate
Patent Information
- Application Number
- PCT/CN2026/073906
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2025-03-27
- Filing Date
- 2026-01-21
- Publication Date
- 2026-10-01
Smart Images
Figure PCTCN2026073906-FTAPPB-I100001 
Figure PCTCN2026073906-FTAPPB-I100002 
Figure PCTCN2026073906-FTAPPB-I100003
Abstract
Description
Dermatological Peptide Drug Conjugate
[0001] CROSS REFERENCE TO RELATED APPLICATIONS
[0002] This application claims the benefit of international application No. PCT / CN2025 / 085266 filed on March 27, 2025, which is incorporated herein by reference in its entirety and for all purposes.FIELD
[0003] The present disclosure relates to dermatological peptide-drug conjugates (PDCs) , synthesis methods thereof, compositions comprising the same, and uses thereof in drug delivery.BACKGROUND
[0004] Hair loss or alopecia represents a prevalent dermatological condition associated with substantial psychological and social burden. Androgenic alopecia (AGA) is one of the most common types of alopecia conditions and it affects both male and female populations. In males, AGA manifests as male-pattern baldness, characterized by progressive recession of the frontotemporal hairline and vertex thinning. Female-pattern hair loss (FPHL) , conversely, typically presents as diffuse crown thinning with preservation of the frontal hairline. Research has established that AGA pathogenesis involves androgen hormones, particularly dihydrotestosterone (DHT) , acting on genetically susceptible hair follicles. Another clinically distinct form of alopecia is Endocrine Therapy-Induced Alopecia (ETIA) , a significant adverse effect observed in patients undergoing endocrine therapies for breast cancer.
[0005] Currently the clinical treatment for alopecia, especially androgenetic alopecia, includes orally administered finasteride and dutasteride, and topical minoxidil treatment. However, many of these treatment options are associated with systemic side effects, such as sexual dysfunction (e.g., decreased libido, erectile dysfunction, and ejaculatory disorders) , hormonal imbalance, mood alterations, cardiovascular effects such as hypotension and tachycardia, as well as dermatological and neurological symptoms. To avoid undesired side effects, local and topical administration is preferred. The efficacy of a topical pharmaceutical formulation is substantially influenced by the rate and depth of skin penetration of the active pharmaceutical ingredient (API) . There remains an unmet need for formulations that enhance transdermal delivery while minimizing blood exposure. Skin is the largest organ of the human body in terms of surface area. As the body’s largest interface with the external environment, skin plays a critical role in regulating molecular transport and barrier function. It serves as the first-defense physical barrier that works alongside the immune system. Successful delivery of therapeutics across the stratum corneum barrier into deeper layers of skin has become a key focus in the research and development of topical treatments and drug products. The effective delivery of bioactive molecules and therapeutic compounds into different skin layers (including stratum corneum, epidermis, dermis) remains a significant challenge in pharmaceutical development. Most bioactive molecules, from small molecules to peptides, proteins and oligonucleotides, struggle to penetrate the skin barrier effectively enough to achieve therapeutic levels.
[0006] Among various approaches to overcome this challenge, peptide carriers have emerged as promising candidates for enhancing the skin penetration of bioactive molecules. This approach has led to the development of peptide-drug conjugates (PDCs) , where the peptide carrier serves as a delivery vehicle chemically linked to the therapeutic payload, including but not limited to small molecules, peptides, proteins and oligonucleotides. While certain peptides demonstrate the ability to penetrate cellular membranes and the stratum corneum, there remains an unmet need for developing more effective skin-penetrating compounds that can achieve targeted delivery.SUMMARY
[0007] In PDCs of the present application, the peptide portion is specifically designed to facilitate penetration across the skin barriers while maintaining the drug's therapeutic activity. Through careful engineering of the peptide sequence and the linking chemistry between the peptide and drug molecule, these conjugates can be optimized to enhance skin penetration, enable targeted delivery to specific skin layers, allow controlled release of the therapeutic payload, and improve the stability and bioavailability of the drug. This innovative approach holds particular promise for delivering a wide range of therapeutic compounds, from small molecules to larger biologics, potentially revolutionizing the field of topical drug delivery.
[0008] The present disclosure provides skin-penetrating peptides and skin-penetrating peptide-drug conjugate (PDC) compounds, compositions comprising the compounds, methods for synthesizing the compounds, and methods of using the compounds and compositions in drug delivery. The skin-penetrating peptides and the skin-penetrating peptide-drug conjugate (PDC) compounds are capable of delivering payloads across biological membranes, especially for delivering payloads to the desired layers of various skin tissues. The skin-penetrating peptides overcome topical delivery barriers, while the linker designs maintain stability and enable controlled release of active components. Therapeutic payloads may include growth factors, hormone modulators, anti-inflammatory agents, and other bioactive compounds for hair growth and follicle health. The conjugates are applicable to various alopecia forms including androgenic alopecia, alopecia areata, and telogen effluvium.
[0009] In one aspect, the present disclosure provides a conjugate or a pharmaceutically acceptable salt thereof, wherein the conjugate comprises a peptide and a payload, with the peptide covalently binds to the payload via a linker, wherein the peptide has the following structure of Formula I:
[0010] R1-W1-X-PP-W2-R2 (Formula I)
[0011] wherein:
[0012] R1 is an N-terminal modification;
[0013] R2 is absent or a C-terminal modification;
[0014] each of W1 and W2 is independently selected from a direct bond or a linking moiety;
[0015] X is absent or a targeting moiety;
[0016] wherein one or more of W1, W2 and X are connected to the linker;
[0017] PP is selected from:
[0018] (1) oligo-arginine or oligo-arginine-analog, or
[0019] (2) oligo-arginine or oligo-arginine-analog, which is implanted with at least one spacer;
[0020] wherein the oligo-arginine is an oligomer of arginine, wherein the arginine can be L or D form; and the oligo-arginine-analog is an oligomer of an arginine analog containing guanidyl;
[0021] wherein one payload can bind to one or more the same or different peptides via the linker, or one or more the same or different payloads can bind to one peptide via the linker;
[0022] wherein the payload is an agent for the treatment of androgenetic alopecia.
[0023] In some preferable embodiments, the peptide has the following structure of Formula II:
[0024] R1-W1-PP -R2 (Formula II)
[0025] wherein:
[0026] R1 is an N-terminal modification;
[0027] R2 is a C-terminal modification;
[0028] W1 is a linking moiety;
[0029] wherein W1 is connected to the linker;
[0030] wherein PP and the payload are the same as defined above.
[0031] In some preferable embodiments, the linker is a cleavable linker or a non-cleavable linker, preferably a cleavable linker, more preferably a linker that can be induced for cleavage and traceless release by reduction, and is preferably selected from the group comprising
[0032] wherein t is an integer of from 1 to 5, preferably 1 to 3;
[0033] and more preferably, the linker is , wherein t is 1, and U is O;
[0034] wherein are preferably for cysteine conjugation, is preferably for lysine conjugation.
[0035] In some preferable embodiments, the payload is selected from the group comprising finasteride, minoxidil, dutasteride and spironolactone, and is preferably finasteride.
[0036] In some preferable embodiments, one payload can bind to 1-2 the same or different peptides via the linker, or 1-2 the same or different payloads can bind to one peptide via the linker; and preferably, one payload binds to one peptide by the linker.
[0037] In some preferable embodiments, R1 is an N-terminal modification selected from the group comprising acetylation, lipidation, PEGylation, cholesterol modification, polycyclic aromatic hydrocarbon modification, glycosylation, fluorination, sulfonation; preferably, acetyl modification, fatty acid modification, and pyrenebutyrate modification.
[0038] In some preferable embodiments, R2 is a C-terminal modification selected from the group comprising amidation, alkylation, lipidation, PEGylation, cholesterol modification, polycyclic aromatic hydrocarbon modification; preferably, NH2.
[0039] In some preferable embodiments, the linking moiety is preferably cysteine or lysine, wherein the cysteine or lysine can be L or D form.
[0040] In some preferable embodiments, the targeting moiety is selected from the group comprising transferrin, a Penetration Accelerating Sequence (PAS) , a Nuclear Localization Signal (NLS) sequence, an Endosomal Escape Enhancer, and a Heparin Sulfate Binding Peptides; and optionally, the targeting moiety is connected to the linker, preferably by Cys or Lys residue in the targeting moiety.
[0041] In some preferable embodiments, the transferrin can be a sequence of Lys-His-Ala-Ile-Tyr-Pro-Arg-His. In some preferable embodiments, the PAS can be a sequence of Pro-Lys-Lys-Lys-Arg-Lys-Val-βAla-Lys-Phe-Phe-Leu-Ile-Pro-Lys-Gly.
[0042] In some preferable embodiments, the Endosomal Escape Enhancer can be selected from the group comprising WEAALAEALAEALAEHLAEALAEALEALAA (GALA) , GLFEAIEGFIENGWEGMIDGWY (INF7) , WEAKLAKALAKALAKHLAKALAKALKACEA (KALA) , GLFHAIAHFIHGGWHGLIHGWYG (H5WYG) , and GLFGAIAGFIENGWEGMIDGWYG (HA2-Derived Peptide) .
[0043] In some preferable embodiments, the Heparin Sulfate Binding Peptides can be selected from the group comprising LRSRTKIIRIR (HBPep) , SPKRKGGSRKYSPTSPTTSPTSKRKYSP (HS-20) , and KHKNKRKT (Platelet Factor 4) .
[0044] In some preferable embodiments, the NLS sequence can be selected from the group comprising PKKKRKV (NLS1) , PKLKRQ (NLS2) , PAAKRVKLD (NLS3) , RPRK, RRARRPRG, GKRKLITSEEERSPAKRGRKS, KGKKGRTQKEKKAARARSKGKN, RKRCAAGVGGGPAGCPAPGSTPLKKPRR, RKPVTAQERQREREEKRRRRQERAKEREKRRQERER, RSGGNHRRNGRGGRGGYNRRNNGYHPY, TLLLRETMNNLGVSDHAVLSRKTPQPY, PGKMDKGEHRQERRDRPY, GKKKKGKPGKRREQRKKKRRT, SANKVTKNKSNSSPYLNKRKGKPGPDS, and VHSHKKKKIPTSPTFTTPKTLTLRRQPKYPRKSAPRRNKLDHY.
[0045] In some preferable embodiments, the oligo-arginine or oligo-arginine-analog is implanted with the spacer in such a way that one spacer is implanted in between every two adjacent residues in the oligo-arginine or oligo-arginine-analog; or in such a way that the spacer and the residues in the oligo-arginine or oligo-arginine-analog collectively form 2 or more unit structures of (X1X2X3) , wherein 0-1 in X1, X2 and X3 is the spacer and the other 2 or 3 are the residues of the oligo-arginine or oligo-arginine-analog.
[0046] In some preferable embodiments, the spacer and the oligo-arginine or oligo-arginine-analog collectively form 2-12, preferably 2-5 unit structures of (X1X2X3) .
[0047] In some preferable embodiments, all the unit structures of (X1X2X3) are the same.
[0048] In some preferable embodiments, the spacer consists of 1-3, preferably 1 residue.
[0049] In some preferable embodiments, the residue in the spacer is selected from the group comprising β-alanine (βAla) , γ-Aminobutyric acid, Aminohexanoic acid (Ahx) , proline, and tryptophan, preferably β-alanine (βAla) ; wherein the residue can be L or D form.
[0050] In some preferable embodiments, the residue in the oligo-arginine-analog is preferably selected from the group comprising 2- (6-guanidylhexyl) amino acetic acid ( , GuanidylC6NHPeptoid) ,2- (4-guanidylbutyl) amino acetic acid ( , GuanidylC4NHPeptoid) , and 2- (7-guanidylheptyl) amino acetic acid ( , GuanidylC7NHPeptoid) .
[0051] In some preferable embodiments, the peptide has the following structures of Formula II, Formula III, Formula IV, Formula V, Formula VI, or Formula VII:
[0052] R1-W1-PP-R2 (Formula II)
[0053] wherein R1, W1, PP, and R2 are the same as defined above, and wherein W1 is connected to the linker; R1-X-PP-R2 (Formula III)
[0054] wherein R1, X, PP, and R2 are the same as defined above; and wherein X is connected to the linker, preferably by Cys or Lys residue in X;
[0055] R1-PP-W2-R2 (Formula IV)
[0056] wherein R1, PP, W2, and R2 are the same as defined above; and wherein W2 is connected to the linker; R1-W1-PP-W2-R2 (Formula V)
[0057] wherein R1, W1, PP, W2, and R2 are the same as defined above, and wherein one or both of W1 and W2 are connected to the linker;
[0058] R1-W1-X-PP-R2 (Formula VI)
[0059] wherein R1, W1, X, PP, and R2 are the same as defined above, and wherein one or both of W1 and X are connected to the linker, and wherein when X is connected to the linker, it is preferably connected by Cys or Lys residue in X;
[0060] R1-X-PP-W2-R2 (Formula VII)
[0061] wherein R1, X, PP, W2, and R2 are the same as defined above, and wherein one or both of X and W2 are connected to the linker, and wherein when X is connected to the linker, it is preferably connected by Cys or Lys residue in X.
[0062] In some embodiments, the PP is oligo-arginine or oligo-arginine-analog.
[0063] In some preferable embodiments, the peptide has the following structure of Formula II:
[0064] R1-W1-PP-R2 (Formula II)
[0065] wherein R1 is a fatty acid modification or acetyl modification, preferably acetyl modification; R2 is NH2; W1 is Cys or Lys, preferably Cys; and the PP is oligo-arginine; and wherein W1 is connected to the linker.
[0066] In some preferable embodiments, the peptide has the following structure of Formula III:
[0067] R1-X-PP-R2 (Formula III)
[0068] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, X is transferrin or PAS, and the PP is oligo-arginine; and
[0069] wherein X is connected to the linker, preferably by Cys or Lys residue in X.
[0070] In some preferable embodiments, the peptide has the following structure of Formula V:
[0071] R1-W1-PP-W2-R2 (Formula V)
[0072] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, each of W1 and W2 is Cys or Lys, and the PP is oligo-arginine; and
[0073] wherein W1 and W2 are connected to the linker.
[0074] In some preferable embodiments, the peptide is selected from the group comprising:
[0075] Ac-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 47) ,
[0076] C8-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 48) ,
[0077] C10-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 49) ,
[0078] C12-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 50) ,
[0079] C14-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 51) ,
[0080] C16-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 52) ,
[0081] C18-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 53) ,
[0082] C20-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 54) ,
[0083] C22-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 55) ,
[0084] Ac-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 56) ,
[0085] C8-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 57) ,
[0086] C10-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 58) ,
[0087] C12-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 59) ,
[0088] C14-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 60) ,
[0089] C16-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 61) ,
[0090] C18-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 62) ,
[0091] C20-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 63) ,
[0092] C22-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 64) ,
[0093] Ac-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 65) ,
[0094] C8-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 66) ,
[0095] C10-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 67) ,
[0096] C12-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 68) ,
[0097] C14-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 69) ,
[0098] C16-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 70) ,
[0099] C18-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 71) ,
[0100] C20-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 72) ,
[0101] C22-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 73) ,
[0102] Ac-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 74) ,
[0103] C8-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 75) ,
[0104] C10-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 76) ,
[0105] C12-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 77) ,
[0106] C14-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 78) ,
[0107] C16-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 79) ,
[0108] C18-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 80) ,
[0109] C20-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 81) ,
[0110] C22-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 82) ,
[0111] Ac-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 83) ,
[0112] C8-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 84) ,
[0113] C10-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 85) ,
[0114] C12-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 86) ,
[0115] C14-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 87) ,
[0116] C16-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 88) ,
[0117] C18-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 89) ,
[0118] C20-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 90) ,
[0119] C22-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 91) ,
[0120] Ac-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 92) ,
[0121] C8-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 93) ,
[0122] C10-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 94) ,
[0123] C12-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 95) ,
[0124] C14-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 96) ,
[0125] C16-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 97) ,
[0126] C18-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 98) ,
[0127] C20-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 99) ,
[0128] C22-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 100) .
[0129] In some embodiments, the PP is oligo-arginine or oligo-arginine-analog implanted with the spacer in such a way that one spacer is implanted in between every two adjacent residues in the oligo-arginine or oligo-arginine-analog, wherein the spacer consists of one residue.
[0130] In some preferable embodiments, the residue is preferably β-alanine.
[0131] In some preferable embodiments, the peptide has the following structure of Formula II:
[0132] R1-W1-PP-R2 (Formula II)
[0133] wherein R1 is a fatty acid modification or acetyl modification, preferably fatty acid modification; R2 is NH2; W1 is Cys or Lys, preferably Cys; and the PP is the same as defined above; and wherein W1 is connected to the linker.
[0134] In some preferable embodiments, the peptide has the following structure of Formula III:
[0135] R1-X-PP-R2 (Formula III)
[0136] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, X is NLS, and the PP is the same as defined above; and wherein X is connected to the linker, preferably by Cys or Lys residue in X.
[0137] In some preferable embodiments, the peptide has the following structure of Formula IV:
[0138] R1-PP-W2-R2 (Formula IV)
[0139] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, W2 is Cys or Lys, and the PP is the same as defined above; and wherein W2 is connected to the linker.
[0140] In some preferable embodiments, the peptide has the following structure of Formula V:
[0141] R1-W1-PP-W2-R2 (Formula V)
[0142] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, each of W1 and W2 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or W2 are connected to the linker. In some preferable embodiments, the peptide has the following structure of Formula VI:
[0143] R1-W1-X-PP-R2 (Formula VI)
[0144] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, W1 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or X are connected to the linker, wherein if X is connected to the linker, it is preferably connected by Cys or Lys residue in X.
[0145] In some preferable embodiments, the peptide has the following structure of Formula I:
[0146] R1-W1-X-PP-W2-R2 (Formula I)
[0147] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, each of W1 and W2 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or W2 and / or X are connected to the linker, wherein if X is connected to the linker, it is preferably connected by Cys or Lys residue in X.
[0148] In some preferable embodiments, the peptide is selected from the group comprising:
[0149] Ac-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 101) ,
[0150] C8-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 102) ,
[0151] C10-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 103) ,
[0152] C12-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 104) ,
[0153] C14-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 105) ,
[0154] C16-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 106) ,
[0155] C18-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 107) ,
[0156] C20-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 108) ,
[0157] C22-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 109) ,
[0158] Ac-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 110) ,
[0159] C8-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 111) ,
[0160] C10-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 112) ,
[0161] C12-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 113) ,
[0162] C14-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 114) ,
[0163] C16-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 115) ,
[0164] C18-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 116) ,
[0165] C20-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 117) ,
[0166] C22-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 118) ,
[0167] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 119) (NLS1-Arg-(βAla-Arg) 5) ,
[0168] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 120) (NLS1-Arg-(βAla-Arg) 5) ,
[0169] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 121) (NLS1-Arg-(βAla-Arg) 5) ,
[0170] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 122) (NLS1-Arg-(βAla-Arg) 5) ,
[0171] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 123) (NLS1-Arg-(βAla-Arg) 5) ,
[0172] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 124) (NLS1-Arg-(βAla-Arg) 5) ,
[0173] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 125) (NLS1-Arg-(βAla-Arg) 5) ,
[0174] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 126) (NLS1-Arg-(βAla-Arg) 5) ,
[0175] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 127) (NLS1-Arg-(βAla-Arg) 5) ,
[0176] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 128) (NLS1-Arg-(βAla-Arg) 5) ,
[0177] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 129) (NLS1-Arg-(βAla-Arg) 5) ,
[0178] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 130) (NLS1-Arg-(βAla-Arg) 5) ,
[0179] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 131) (NLS1-Arg-(βAla-Arg) 5) ,
[0180] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 132) (NLS1-Arg-(βAla-Arg) 5) ,
[0181] C16-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 133) (NLS1-Arg-(βAla-Arg) 5) ,
[0182] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 134) (NLS1-Arg-(βAla-Arg) 5) ,
[0183] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 135) (NLS1-Arg-(βAla-Arg) 5) ,
[0184] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 136) (NLS1-Arg-(βAla-Arg) 5) ,
[0185] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 137) (NLS1-Arg-(βAla-Arg) 4) ,
[0186] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 138) (NLS1-Arg-(βAla-Arg) 4) ,
[0187] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 139) (NLS1-Arg-(βAla-Arg) 4) ,
[0188] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 140) (NLS1-Arg-(βAla-Arg) 4) ,
[0189] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 141) (NLS1-Arg-(βAla-Arg) 4) ,
[0190] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 142) (NLS1-Arg-(βAla-Arg) 4) ,
[0191] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 143) (NLS1-Arg-(βAla-Arg) 4) ,
[0192] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 144) (NLS1-Arg-(βAla-Arg) 4) ,
[0193] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 145) (NLS1-Arg-(βAla-Arg) 4) ,
[0194] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 146) (NLS1-Arg-(βAla-Arg) 4) ,
[0195] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 147) (NLS1-Arg-(βAla-Arg) 4) ,
[0196] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 148) (NLS1-Arg-(βAla-Arg) 4) ,
[0197] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 149) (NLS1-Arg-(βAla-Arg) 4) ,
[0198] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 150) (NLS1-Arg-(βAla-Arg) 4) ,
[0199] C16-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 151) (NLS1-Arg-(βAla-Arg) 4) ,
[0200] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 152) (NLS1-Arg-(βAla-Arg) 4) ,
[0201] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 153) (NLS1-Arg-(βAla-Arg) 4) ,
[0202] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 154) (NLS1-Arg-(βAla-Arg) 4) ,
[0203] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 155) (NLS2-Arg-(βAla-Arg) 4) ,
[0204] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 156) (NLS2-Arg-(βAla-Arg) 4) ,
[0205] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 157) (NLS2-Arg-(βAla-Arg) 4) ,
[0206] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 158) (NLS2-Arg-(βAla-Arg) 4) ,
[0207] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 159) (NLS2-Arg-(βAla-Arg) 4) ,
[0208] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 160) (NLS2-Arg-(βAla-Arg) 4) ,
[0209] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 161) (NLS2-Arg-(βAla-Arg) 4) ,
[0210] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 162) (NLS2-Arg-(βAla-Arg) 4) ,
[0211] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 163) (NLS2-Arg-(βAla-Arg) 4) ,
[0212] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 164) (NLS2-Arg-(βAla-Arg) 4) ,
[0213] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 165) (NLS2-Arg-(βAla-Arg) 4) ,
[0214] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 166) (NLS2-Arg-(βAla-Arg) 4) ,
[0215] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 167) (NLS2-Arg-(βAla-Arg) 4) ,
[0216] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 168) (NLS2-Arg-(βAla-Arg) 4) ,
[0217] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 169) (NLS2-Arg-(βAla-Arg) 4) ,
[0218] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 170) (NLS2-Arg-(βAla-Arg) 4) ,
[0219] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 171) (NLS2-Arg-(βAla-Arg) 4) ,
[0220] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 172) (NLS2-Arg-(βAla-Arg) 4) ,
[0221] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 173) (NLS3-Arg- (βAla-Arg) 4) ,
[0222] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 174) (NLS3-Arg- (βAla-Arg) 4) ,
[0223] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 175) (NLS3-Arg- (βAla-Arg) 4) ,
[0224] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 176) (NLS3-Arg- (βAla-Arg) 4) ,
[0225] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 177) (NLS3-Arg- (βAla-Arg) 4) ,
[0226] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 178) (NLS3-Arg- (βAla-Arg) 4) ,
[0227] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 179) (NLS3-Arg- (βAla-Arg) 4) ,
[0228] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 180) (NLS3-Arg- (βAla-Arg) 4) ,
[0229] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 181) (NLS3-Arg- (βAla-Arg) 4) ,
[0230] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 182) (NLS3-Arg- (βAla-Arg) 4) ,
[0231] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 183) (NLS3-Arg- (βAla-Arg) 4) ,
[0232] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 184) (NLS3-Arg- (βAla-Arg) 4) ,
[0233] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 185) (NLS3-Arg- (βAla-Arg) 4) ,
[0234] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 186) (NLS3-Arg- (βAla-Arg) 4) ,
[0235] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 187) (NLS3-Arg- (βAla-Arg) 4) ,
[0236] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 188) (NLS3-Arg- (βAla-Arg) 4) ,
[0237] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 189) (NLS3-Arg- (βAla-Arg) 4) ,
[0238] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 190) (NLS3-Arg- (βAla-Arg) 4) ,
[0239] Ac-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 191) ,
[0240] C8-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 192) ,
[0241] C10-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 193) ,
[0242] C12-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 194) ,
[0243] C14-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 195) ,
[0244] C16-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 196) ,
[0245] C18-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 197) ,
[0246] C20-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 198) ,
[0247] C22-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 199) ,
[0248] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 200) (NLS1-Arg- (βAla-Arg) 5)
[0249] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 201) (NLS1-Arg- (βAla-Arg) 5)
[0250] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 202) (NLS1-Arg- (βAla-Arg) 5)
[0251] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 203) (NLS1-Arg- (βAla-Arg) 5)
[0252] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 204) (NLS1-Arg- (βAla-Arg) 5)
[0253] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 205) (NLS1-Arg- (βAla-Arg) 5)
[0254] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 206) (NLS1-Arg- (βAla-Arg) 5)
[0255] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 207) (NLS1-Arg- (βAla-Arg) 5)
[0256] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 208) (NLS1-Arg- (βAla-Arg) 5)
[0257] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 209) (NLS1-Arg- (βAla-Arg) 4) ,
[0258] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 210) (NLS1-Arg- (βAla-Arg) 4) ,
[0259] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 211) (NLS1-Arg- (βAla-Arg) 4) ,
[0260] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 212) (NLS1-Arg- (βAla-Arg) 4) ,
[0261] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 213) (NLS1-Arg- (βAla-Arg) 4) ,
[0262] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 214) (NLS1-Arg- (βAla-Arg) 4) ,
[0263] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 215) (NLS1-Arg- (βAla-Arg) 4) ,
[0264] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 216) (NLS1-Arg- (βAla-Arg) 4) ,
[0265] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 217) (NLS1-Arg- (βAla-Arg) 4) ,
[0266] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 218) (NLS2-Arg-(βAla-Arg) 4) ,
[0267] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 219) (NLS2-Arg-(βAla-Arg) 4) ,
[0268] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 220) (NLS2-Arg-(βAla-Arg) 4) ,
[0269] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 221) (NLS2-Arg-(βAla-Arg) 4) ,
[0270] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 222) (NLS2-Arg-(βAla-Arg) 4) ,
[0271] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 223) (NLS2-Arg-(βAla-Arg) 4) ,
[0272] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 224) (NLS2-Arg-(βAla-Arg) 4) ,
[0273] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 225) (NLS2-Arg-(βAla-Arg) 4) ,
[0274] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 226) (NLS2-Arg-(βAla-Arg) 4) ,
[0275] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 227) (NLS3-Arg- (βAla-Arg) 4) ,
[0276] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 228) (NLS3-Arg- (βAla-Arg) 4) ,
[0277] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 229) (NLS3-Arg- (βAla-Arg) 4) ,
[0278] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 230) (NLS3-Arg- (βAla-Arg) 4) ,
[0279] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 231) (NLS3-Arg- (βAla-Arg) 4) ,
[0280] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 232) (NLS3-Arg- (βAla-Arg) 4) ,
[0281] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 233) (NLS3-Arg- (βAla-Arg) 4) ,
[0282] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 234) (NLS3-Arg- (βAla-Arg) 4) ,
[0283] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 235) (NLS3-Arg- (βAla-Arg) 4) ,
[0284] Acetyl- (GuanidylC6NHPeptoid-Ahx) 7GuanidylC6NHPeptoid-Cys-NH2, (SEQ. ID No. 236) C18-Ahx-GuanidylC6NHPeptoid- (Ahx-GuanidylC6NHPeptoid) 7-Cys-NH2 (SEQ. ID No. 237) .
[0285] In some embodiments, the PP is oligo-arginine or oligo-arginine-analog implanted with the spacer in such a way that the spacer and the oligo-arginine or oligo-arginine-analog collectively form the same unit structures of (X1X2X3) , wherein X2 is the spacer and X1 and X3 are arginine or arginine-analog, wherein the spacer consists of one residue.
[0286] In some preferable embodiments, wherein the residue is preferably Aminohexanoic acid or β-alanine.
[0287] In some preferable embodiments, the peptide has the following structure of Formula II:
[0288] R1-W1-PP-R2 (Formula II)
[0289] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, and the PP is the same as defined above; and wherein W1 is connected to the linker.
[0290] In some preferable embodiments, the peptide has the following structure of Formula III:
[0291] R1-X-PP-R2 (Formula III)
[0292] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, X is NLS, and the PP is the same as defined above; and wherein X is connected to the linker, preferably by Cys or Lys residue in X.
[0293] In some preferable embodiments, the peptide has the following structure of Formula IV:
[0294] R1-PP-W2-R2 (Formula IV)
[0295] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, and the PP is the same as defined above; and wherein W2 is connected to the linker.
[0296] In some preferable embodiments, the peptide has the following structure of Formula V:
[0297] R1-W1-PP-W2-R2 (Formula V)
[0298] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, each of W1 and W2 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or W2 are connected to the linker. In some preferable embodiments, the peptide has the following structure of Formula VI:
[0299] R1-W1-X-PP-R2 (Formula VI)
[0300] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, W1 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or X are connected to the linker, wherein if X is connected to the linker, it is preferably connected by Cys or Lys residue in X.
[0301] In some preferable embodiments, the peptide has the following structure of Formula I:
[0302] R1-W1-X-PP-W2-R2 (Formula I)
[0303] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, each of W1 and W2 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or W2 and / or X are connected to the linker, wherein if X is connected to the linker, it is preferably connected by Cys or Lys residue in X.
[0304] In some preferable embodiments, the peptide is selected from the group comprising:
[0305] Ac- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 238) ,
[0306] C8- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 239) ,
[0307] C10- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 240) ,
[0308] C12- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 241) ,
[0309] C14- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 242) ,
[0310] C16- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 243) ,
[0311] C18- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 244) ,
[0312] C20- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 245) ,
[0313] C22- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 246) ,
[0314] Ac- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 247) ,
[0315] C8- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 248) ,
[0316] C10- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 249) ,
[0317] C12- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 250) ,
[0318] C14- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 251) ,
[0319] C16- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 252) ,
[0320] C18- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 253) ,
[0321] C20- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 254) ,
[0322] C22- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 255) ,
[0323] Ac- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 256) ,
[0324] C8- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 257) ,
[0325] C10- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 258) ,
[0326] C12- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 259) ,
[0327] C14- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 260) ,
[0328] C16- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 261) ,
[0329] C18- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 262) ,
[0330] C20- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 263) ,
[0331] C22- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 264) ,
[0332] Ac- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 265) ,
[0333] C8- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 266) ,
[0334] C10- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 267) ,
[0335] C12- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 268) ,
[0336] C14- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 269) ,
[0337] C16- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 270) ,
[0338] C18- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 271) ,
[0339] C20- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 272) ,
[0340] C22- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 273) ,
[0341] Ac-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 274) ,
[0342] C8-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 275) ,
[0343] C10-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 276) ,
[0344] C12-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 277) ,
[0345] C14-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 278) ,
[0346] C16-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 279) ,
[0347] C18-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 280) ,
[0348] C20-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 281) ,
[0349] C22-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 282) ,
[0350] Ac-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 283) ,
[0351] C8-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 284) ,
[0352] C10-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 285) ,
[0353] C12-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 286) ,
[0354] C14-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 287) ,
[0355] C16-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 288) ,
[0356] C18-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 289) ,
[0357] C20-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 290) ,
[0358] C22-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 291) ,
[0359] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 292) (NLS1- (Arg-βAla-Arg) 4) ,
[0360] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 293) (NLS1- (Arg-βAla-Arg) 4) ,
[0361] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 294) (NLS1-(Arg-βAla-Arg) 4) ,
[0362] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 295) (NLS1-(Arg-βAla-Arg) 4) ,
[0363] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 296) (NLS1-(Arg-βAla-Arg) 4) ,
[0364] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 297) (NLS1-(Arg-βAla-Arg) 4) ,
[0365] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 298) (NLS1-(Arg-βAla-Arg) 4) ,
[0366] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 299) (NLS1-(Arg-βAla-Arg) 4) ,
[0367] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 300) (NLS1-(Arg-βAla-Arg) 4) ,
[0368] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 301) (NLS1- (Arg-βAla-Arg) 4) ,
[0369] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 302) (NLS1- (Arg-βAla-Arg) 4) ,
[0370] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 303) (NLS1-(Arg-βAla-Arg) 4) ,
[0371] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 304) (NLS1-(Arg-βAla-Arg) 4) ,
[0372] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 305) (NLS1- (Arg-βAla-Arg) 4) ,
[0373] C16-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 306) (NLS1- (Arg-βAla-Arg) 4) ,
[0374] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 307) (NLS1- (Arg-βAla-Arg) 4) ,
[0375] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 308) (NLS1- (Arg-βAla-Arg) 4) ,
[0376] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 309) (NLS1-(Arg-βAla-Arg) 4) ,
[0377] Ac-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 310) ,
[0378] C8-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 311) ,
[0379] C10-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 312) ,
[0380] C12-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 313) ,
[0381] C14-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 314) ,
[0382] C16-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 315) ,
[0383] C18-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 316) ,
[0384] C20-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 317) ,
[0385] C22-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 318) ,
[0386] Ac-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 319) ,
[0387] C8-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 320) ,
[0388] C10-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 321) ,
[0389] C12-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 322
[0390] C14-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 323) ,
[0391] C16-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 324) ,
[0392] C18-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 325) ,
[0393] C20-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 326) ,
[0394] C22-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 327
[0395] Ac-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 328) ,
[0396] C8-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 329) ,
[0397] C10-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 330) ,
[0398] C12-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 331
[0399] C14-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 332) ,
[0400] C16-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 333) ,
[0401] C18-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 334) ,
[0402] C20-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 335) ,
[0403] C22-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 336) ,
[0404] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 337) (NLS1- (Arg-βAla-Arg) 4) ,
[0405] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 338) (NLS1- (Arg-βAla-Arg) 4) ,
[0406] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 339) (NLS1- (Arg-βAla-Arg) 4) ,
[0407] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 340) (NLS1- (Arg-βAla-Arg) 4) ,
[0408] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 341) (NLS1- (Arg-βAla-Arg) 4) ,
[0409] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 342) (NLS1- (Arg-βAla-Arg) 4) ,
[0410] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 343) (NLS1- (Arg-βAla-Arg) 4) ,
[0411] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 344) (NLS1- (Arg-βAla-Arg) 4) ,
[0412] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 345) (NLS1- (Arg-βAla-Arg) 4) .
[0413] In some embodiments, the PP is oligo-arginine or oligo-arginine-analog implanted with the spacer in such a way that the spacer and the oligo-arginine or oligo-arginine-analog collectively form the same unit structures of (X1X2X3) , wherein X1 is proline and X2 and X3 are arginine or arginine-analog, wherein proline and arginine can be L or D form.
[0414] In some preferable embodiments, the peptide has the following structure of Formula II:
[0415] R1-W1-PP-R2 (Formula II)
[0416] wherein R1 is a fatty acid modification or acetyl modification, R2 is absent or NH2, W1 is Cys or Lys, and the PP is the same as defined above; and wherein W1 is connected to the linker.
[0417] In some preferable embodiments, the peptide has the following structure of Formula III:
[0418] R1-X-PP-R2 (Formula III)
[0419] wherein R1 is a fatty acid modification or acetyl modification, R2 is absent or NH2, X is NLS, and the PP is the same as defined above; preferably, the NLS is selected from NLS1, NLS2 or NLS3; and wherein X is connected to the linker, preferably by Cys or Lys residue in X.
[0420] In some preferable embodiments, the peptide has the following structure of Formula V:
[0421] R1-W1-PP-W2-R2 (Formula V)
[0422] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2 or absent, each of W1 and W2 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or W2 are connected to the linker.
[0423] In some preferable embodiments, the peptide has the following structure of Formula VI:
[0424] R1-W1-X-PP-R2 (Formula VI)
[0425] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2 or absent, W1 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or X are connected to the linker, wherein if X is connected to the linker, it is preferably connected by Cys or Lys residue in X.
[0426] In some preferable embodiments, the peptide has the following structure of Formula I:
[0427] R1-W1-X-PP-W2-R2 (Formula I)
[0428] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2 or absent, each of W1 and W2 is Cys or Lys, and the PP is the same as defined above; and wherein W1 and / or W2 and / or X are connected to the linker, wherein if X is connected to the linker, it is preferably connected by Cys or Lys residue in X.
[0429] In some preferable embodiments, the peptide is selected from the group comprising:
[0430] Ac-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 346) ,
[0431] C8-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 347) ,
[0432] C10-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 348) ,
[0433] C12-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 349) ,
[0434] C14-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 350) ,
[0435] C16-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 351) ,
[0436] C18-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 352) ,
[0437] C20-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 353) ,
[0438] C22-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 354) ,
[0439] Ac-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 355) ,
[0440] C8-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 356) ,
[0441] C10-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 357) ,
[0442] C12-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 358) ,
[0443] C14-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 359) ,
[0444] C16-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 360) ,
[0445] C18-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 361) ,
[0446] C20-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 362) ,
[0447] C22-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 363) ,
[0448] Ac-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 364) ,
[0449] C8-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 365) ,
[0450] C10-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 366) ,
[0451] C12-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 367) ,
[0452] C14-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 368) ,
[0453] C16-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 369) ,
[0454] C18-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 370) ,
[0455] C20-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 371) ,
[0456] C22-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 372) ,
[0457] Ac-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 373) ,
[0458] C8-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 374) ,
[0459] C10-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 375) ,
[0460] C12-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 376) ,
[0461] C14-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 377) ,
[0462] C16-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 378) ,
[0463] C18-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 379) ,
[0464] C20-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 380) ,
[0465] C22-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 381) ,
[0466] Ac-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 382) ,
[0467] C8-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 383) ,
[0468] C10-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 384) ,
[0469] C12-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 385) ,
[0470] C14-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 386) ,
[0471] C16-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 387) ,
[0472] C18-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 388) ,
[0473] C20-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 389) ,
[0474] C22-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 390) ,
[0475] Ac-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 391) ,
[0476] C8-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 392) ,
[0477] C10-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 393) ,
[0478] C12-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 394) ,
[0479] C14-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 395) ,
[0480] C16-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 396) ,
[0481] C18-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 397) ,
[0482] C20-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 398) ,
[0483] C22-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 399) ,
[0484] Ac-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 400) ,
[0485] C8-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 401) ,
[0486] C10-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 402) ,
[0487] C12-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 403) ,
[0488] C14-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 404) ,
[0489] C16-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 405) ,
[0490] C18-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 406) ,
[0491] C20-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 407) ,
[0492] C22-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 408) ,
[0493] Ac-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 409) ,
[0494] C8-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 410) ,
[0495] C10-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 411) ,
[0496] C12-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 412) ,
[0497] C14-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 413) ,
[0498] C16-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 414) ,
[0499] C18-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 415) ,
[0500] C20-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 416) ,
[0501] C22-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 417) ,
[0502] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 418) (NLS1-pRR3) , C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 419) (NLS1-pRR3) ,
[0503] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 420) (NLS1-pRR3) ,
[0504] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 421) (NLS1-pRR3) ,
[0505] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 422) (NLS1-pRR3) ,
[0506] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 423) (NLS1-pRR3) ,
[0507] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 424 (NLS1-pRR3) ,
[0508] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 425) (NLS1-pRR3) ,
[0509] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 426) (NLS1-pRR3) ,
[0510] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 427) (NLS1-pRR3) ,
[0511] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 428) (NLS1-pRR3) ,
[0512] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 429) (NLS1-pRR3) ,
[0513] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 430) (NLS1-pRR3) ,
[0514] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 431) (NLS1-pRR3) ,
[0515] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 432) (NLS1-pRR3) ,
[0516] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 433) (NLS1-pRR3) ,
[0517] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 434) (NLS2-pRR3) ,
[0518] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 435) (NLS2-pRR3) ,
[0519] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 436) (NLS2-pRR3) ,
[0520] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 437) (NLS2-pRR3) ,
[0521] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 438) (NLS2-pRR3) ,
[0522] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 439) (NLS2-pRR3) ,
[0523] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 440) (NLS2-pRR3) ,
[0524] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 441) (NLS2-pRR3) ,
[0525] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 442) (NLS2-pRR3) ,
[0526] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 443) (NLS2-pRR3) ,
[0527] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 444) (NLS2-pRR3) ,
[0528] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 445) (NLS2-pRR3) ,
[0529] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 446) (NLS2-pRR3) ,
[0530] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 447) (NLS2-pRR3) ,
[0531] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 448) (NLS2-pRR3) ,
[0532] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 449) (NLS2-pRR3) ,
[0533] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 450) (NLS2-pRR3) ,
[0534] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 451) (NLS2-pRR3) ,
[0535] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 452) (NLS3-pRR3) ,
[0536] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 453) (NLS3-pRR3) ,
[0537] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 454) (NLS3-pRR3) ,
[0538] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 455) (NLS3-pRR3) ,
[0539] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 456) (NLS3-pRR3) ,
[0540] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 457) (NLS3-pRR3) ,
[0541] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 458) (NLS3-pRR3) ,
[0542] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 459) (NLS3-pRR3) ,
[0543] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 460) (NLS3-pRR3) ,
[0544] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 461) (NLS3-pRR3) ,
[0545] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 462) (NLS3-pRR3) ,
[0546] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 463) (NLS3-pRR3) ,
[0547] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 464) (NLS3-pRR3) ,
[0548] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 465) (NLS3-pRR3) ,
[0549] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 466) (NLS3-pRR3) ,
[0550] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 467) (NLS3-pRR3) ,
[0551] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 468) (NLS3-pRR3) ,
[0552] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 469) (NLS3-pRR3) ,
[0553] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 470) (NLS1-pRR4) ,
[0554] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 471) (NLS1-pRR4) ,
[0555] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 472) (NLS1-pRR4) ,
[0556] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 473) (NLS1-pRR4) ,
[0557] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 474) (NLS1-pRR4) ,
[0558] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 475) (NLS1-pRR4) ,
[0559] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 476) (NLS1-pRR4) ,
[0560] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 477) (NLS1-pRR4) ,
[0561] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 478) (NLS1-pRR4) ,
[0562] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 479) (NLS1-pRR4) ,
[0563] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 480) (NLS1-pRR4) ,
[0564] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 481) (NLS1-pRR4) ,
[0565] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 482) (NLS1-pRR4) ,
[0566] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 483) (NLS1-pRR4) ,
[0567] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 484) (NLS1-pRR4) ,
[0568] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 485) (NLS1-pRR4) ,
[0569] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 486) (NLS2-pRR4) ,
[0570] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 487) (NLS2-pRR4) ,
[0571] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 488) (NLS2-pRR4) ,
[0572] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 489) (NLS2-pRR4) ,
[0573] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 490) (NLS2-pRR4) ,
[0574] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 491) (NLS2-pRR4) ,
[0575] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 492) (NLS2-pRR4) ,
[0576] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 493) (NLS2-pRR4) ,
[0577] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 494) (NLS2-pRR4) ,
[0578] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 495) (NLS2-pRR4) ,
[0579] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 496) (NLS2-pRR4) ,
[0580] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 497) (NLS2-pRR4) ,
[0581] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 498) (NLS2-pRR4) ,
[0582] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 499) (NLS2-pRR4) ,
[0583] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 500) (NLS2-pRR4) ,
[0584] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 501) (NLS2-pRR4) ,
[0585] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 502) (NLS2-pRR4) ,
[0586] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 503) (NLS2-pRR4) ,
[0587] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 504) (NLS3-pRR4) ,
[0588] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 505) (NLS3-pRR4) ,
[0589] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 506) (NLS3-pRR4) ,
[0590] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 507) (NLS3-pRR4) ,
[0591] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 508) (NLS3-pRR4) ,
[0592] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 509) (NLS3-pRR4) ,
[0593] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 510) (NLS3-pRR4) ,
[0594] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 511) (NLS3-pRR4) ,
[0595] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 512) (NLS3-pRR4) ,
[0596] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 513) (NLS3-pRR4) ,
[0597] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 514) (NLS3-pRR4) ,
[0598] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 515) (NLS3-pRR4) ,
[0599] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 516) (NLS3-pRR4) ,
[0600] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 517) (NLS3-pRR4) ,
[0601] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 518) (NLS3-pRR4) ,
[0602] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 519) (NLS3-pRR4) ,
[0603] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 520) (NLS3-pRR4) ,
[0604] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 521) (NLS3-pRR4) ,
[0605] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 522) (NLS1-pRR5) ,
[0606] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 523) (NLS1-pRR5) ,
[0607] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 524) (NLS1-pRR5) ,
[0608] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 525) (NLS1-pRR5) ,
[0609] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 526) (NLS1-pRR5) ,
[0610] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 527) (NLS1-pRR5) ,
[0611] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 528) (NLS1-pRR5) ,
[0612] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 529) (NLS1-pRR5) ,
[0613] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 530) (NLS1-pRR5) ,
[0614] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 531) (NLS1-pRR5) ,
[0615] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 532) (NLS1-pRR5) ,
[0616] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 533) (NLS1-pRR5) ,
[0617] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 534) (NLS1-pRR5) ,
[0618] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 535) (NLS1-pRR5) ,
[0619] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 536) (NLS1-pRR5) ,
[0620] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 537) (NLS1-pRR5) ,
[0621] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 538) (NLS2-pRR5) ,
[0622] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 539) ,
[0623] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 540) ,
[0624] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 541) ,
[0625] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 542) ,
[0626] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 543) ,
[0627] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 544) ,
[0628] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 545) ,
[0629] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 546) ,
[0630] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 547) (NLS2-pRR5) ,
[0631] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 548) (NLS2-pRR5) ,
[0632] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 549) (NLS2-pRR5) ,
[0633] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 550) (NLS2-pRR5) ,
[0634] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 551) (NLS2-pRR5) ,
[0635] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 552) (NLS2-pRR5) ,
[0636] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 553) (NLS2-pRR5) ,
[0637] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 554) (NLS2-pRR5) ,
[0638] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 555) (NLS2-pRR5) ,
[0639] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 556) (NLS3-pRR5) ,
[0640] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 557) (NLS3-pRR5) ,
[0641] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 558) (NLS3-pRR5) ,
[0642] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 559) (NLS3-pRR5) ,
[0643] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 560) (NLS3-pRR5) ,
[0644] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 561) (NLS3-pRR5) ,
[0645] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 562) (NLS3-pRR5) ,
[0646] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 563) (NLS3-pRR5) ,
[0647] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 564) (NLS3-pRR5) ,
[0648] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 565) (NLS3-pRR5) ,
[0649] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 566) (NLS3-pRR5) ,
[0650] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 567) (NLS3-pRR5) ,
[0651] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 568) (NLS3-pRR5) ,
[0652] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 569) (NLS3-pRR5) ,
[0653] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 570) (NLS3-pRR5) ,
[0654] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 571) (NLS3-pRR5) ,
[0655] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 572) (NLS3-pRR5) ,
[0656] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 573) (NLS3-pRR5) ,
[0657] Ac-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 574) ,
[0658] C8-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 575) ,
[0659] C10-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 576) ,
[0660] C12-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 577) ,
[0661] C14-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 578) ,
[0662] C16-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 579) ,
[0663] C18-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 580) ,
[0664] C20-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 581) ,
[0665] C22-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 582) ,
[0666] Ac-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 583) ,
[0667] C8-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 584) ,
[0668] C10-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 585) ,
[0669] C12-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 586) ,
[0670] C14-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 587) ,
[0671] C16-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 588) ,
[0672] C18-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 589) ,
[0673] C20-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 590) ,
[0674] C22-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 591) ,
[0675] Ac-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 592) ,
[0676] C8-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 593) ,
[0677] C10-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 594) ,
[0678] C12-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 595) ,
[0679] C14-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 596) ,
[0680] C16-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 597) ,
[0681] C18-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 598) ,
[0682] C20-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 599) ,
[0683] C22-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 600) ,
[0684] Ac-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 601) ,
[0685] C8-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 602) ,
[0686] C10-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 603) ,
[0687] C12-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 604) ,
[0688] C14-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 605) ,
[0689] C16-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 606) ,
[0690] C18-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 607) ,
[0691] C20-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 608) ,
[0692] C22-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 609) ,
[0693] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 610) (NLS1-pRR3) ,
[0694] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 611) (NLS1-pRR3) ,
[0695] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 612) (NLS1-pRR3) ,
[0696] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 613) (NLS1-pRR3) ,
[0697] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 614) (NLS1-pRR3) ,
[0698] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 615) (NLS1-pRR3) ,
[0699] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 616) (NLS1-pRR3) ,
[0700] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 617) (NLS1-pRR3) ,
[0701] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 618) (NLS2-pRR3) ,
[0702] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 619) (NLS2-pRR3) ,
[0703] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 620) (NLS2-pRR3) ,
[0704] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 621) (NLS2-pRR3) ,
[0705] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 622) (NLS2-pRR3) ,
[0706] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 623) (NLS2-pRR3) ,
[0707] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 624) (NLS2-pRR3) ,
[0708] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 625) (NLS2-pRR3) ,
[0709] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 626) (NLS2-pRR3) ,
[0710] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 627) (NLS3-pRR3) ,
[0711] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 628) (NLS3-pRR3) ,
[0712] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 629) (NLS3-pRR3) ,
[0713] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 630) (NLS3-pRR3) ,
[0714] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 631) (NLS3-pRR3) ,
[0715] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 632) (NLS3-pRR3) ,
[0716] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 633) (NLS3-pRR3) ,
[0717] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 634) (NLS3-pRR3) ,
[0718] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 635) (NLS3-pRR3) ,
[0719] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 636) (NLS1-pRR4) ,
[0720] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 637) (NLS1-pRR4) ,
[0721] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 638) (NLS1-pRR4) ,
[0722] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 639) (NLS1-pRR4) ,
[0723] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 640) (NLS1-pRR4) ,
[0724] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 641) (NLS1-pRR4) ,
[0725] C20-CysPro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 642) (NLS1-pRR4) ,
[0726] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 643) (NLS1-pRR4) ,
[0727] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 644) (NLS2-pRR4) ,
[0728] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 645) (NLS2-pRR4) ,
[0729] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 646) (NLS2-pRR4) ,
[0730] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 647) (NLS2-pRR4) ,
[0731] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 648) (NLS2-pRR4) ,
[0732] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 649) (NLS2-pRR4) ,
[0733] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 650) (NLS2-pRR4) ,
[0734] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 651) (NLS2-pRR4) ,
[0735] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 652) (NLS2-pRR4) ,
[0736] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 653) (NLS3-pRR4) ,
[0737] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 654) (NLS3-pRR4) ,
[0738] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 655) (NLS3-pRR4) ,
[0739] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 656) (NLS3-pRR4) ,
[0740] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 657) (NLS3-pRR4) ,
[0741] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 658) (NLS3-pRR4) ,
[0742] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 659) (NLS3-pRR4) ,
[0743] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 660) (NLS3-pRR4) ,
[0744] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 661) (NLS3-pRR4) ,
[0745] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 662) (NLS1-pRR5) ,
[0746] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 663) (NLS1-pRR5) ,
[0747] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 664) (NLS1-pRR5) ,
[0748] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 665) (NLS1-pRR5) ,
[0749] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 666) (NLS1-pRR5) ,
[0750] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 667) (NLS1-pRR5) ,
[0751] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 668) (NLS1-pRR5) ,
[0752] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 669) (NLS1-pRR5) ,
[0753] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 670) (NLS2-pRR5) ,
[0754] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 671) (NLS2-pRR5) ,
[0755] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 672) (NLS2-pRR5) ,
[0756] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 673) (NLS2-pRR5) ,
[0757] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 674) (NLS2-pRR5) ,
[0758] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 675) (NLS2-pRR5) ,
[0759] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 676) (NLS2-pRR5) ,
[0760] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 677) (NLS2-pRR5) ,
[0761] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 678) (NLS2-pRR5) ,
[0762] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 679) (NLS3-pRR5) ,
[0763] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 680) (NLS3-pRR5) ,
[0764] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 681) (NLS3-pRR5) ,
[0765] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 682) (NLS3-pRR5) ,
[0766] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 683) (NLS3-pRR5) ,
[0767] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 684) (NLS3-pRR5) ,
[0768] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 685) (NLS3-pRR5) ,
[0769] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 686) (NLS3-pRR5) ,
[0770] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 687) (NLS3-pRR5) .
[0771] In some embodiments, the PP is oligo-arginine or oligo-arginine-analog implanted with the spacer in such a way that the spacer and the oligo-arginine or oligo-arginine-analog collectively form the same or different unit structures of (X1X2X3) , wherein 1 in X1, X2 and X3 is the spacer and the other 2 are the residues of the oligo-arginine or oligo-arginine-analog, and the spacer consists of 1 residue.
[0772] In some preferable embodiments, the residue of the spacer is preferably tryptophan.
[0773] In some preferable embodiments, the peptide has the following structure of Formula II:
[0774] R1-W1-PP-R2 (Formula II)
[0775] wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, W1 is Cys or Lys, and the PP is the same as defined above; and wherein W1 is connected to the linker.
[0776] In some preferable embodiments, the peptide is selected from the group comprising:
[0777] C18-Cys-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg-CONH2 (SEQ. ID No. 688) .
[0778] In some preferable embodiments, the payload is Finasteride or Minoxidil, and the conjugate is preferably selected from the PDCs in Table 2 and in the lists following Table 2.
[0779] In one aspect, the present disclosure provides a pharmaceutical composition comprising the conjugate or pharmaceutically acceptable salt thereof mentioned above, and a pharmaceutical excipient, preferably the pharmaceutical composition is selected from the group comprising ointment, cream, solution, tincture, gel, spray, powder, foam, spirit, powder, lotion, oil, emulsion, suspension, paste, film, and aerosol.
[0780] In one aspect, the present disclosure provides a cosmetic composition comprising the conjugate or cosmetically acceptable salt thereof mentioned above, preferably the cosmetic composition is selected from the group comprising skin lotion, milk lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, powder, hair tonic, hear cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, solgel, emulsion, oil, wax and aerosol.
[0781] In one aspect, the present disclosure provides the conjugate or pharmaceutically acceptable salt thereof or the pharmaceutical composition mentioned above for use in the treatment of androgenetic alopecia. In one aspect, the present disclosure provides the conjugate or cosmetically acceptable salt thereof or the cosmetic composition mentioned above for use in cosmetic application.
[0782] In one aspect, the present disclosure provides use of the conjugate or pharmaceutically acceptable salt thereof or the pharmaceutical composition mentioned above for the manufacture of a medicament for the treatment of androgenetic alopecia.
[0783] In one aspect, the present disclosure provides use of the conjugate or cosmetically acceptable salt thereof or the cosmetic composition mentioned above for the manufacture of a cosmetic.
[0784] In one aspect, the present disclosure provides a method for treating androgenetic alopecia, comprising administering the conjugate or pharmaceutically acceptable salt thereof or the pharmaceutical composition mentioned above to a subject in need thereof.
[0785] In some preferable embodiments, the conjugate or pharmaceutically acceptable salt thereof or the pharmaceutical composition is topically administered to the subject.
[0786] In some preferable embodiments, the conjugate or pharmaceutically acceptable salt thereof or the pharmaceutical composition topically administered to the skin of the subject.
[0787] In one aspect, the present disclosure provides a cosmetic method, comprising topically applying the conjugate or cosmetically acceptable salt thereof or the cosmetic composition mentioned above to a subject in need thereof.BRIEF DESCRIPTION OF THE DRAWINGS
[0788] FIGS. 1A and 1B show HaCaT cellular uptake of select peptides for 1 hour and 6 hours, respectively.
[0789] FIGS. 2A and 2B show HaCaT cellular uptake of select peptides for 1 hour and 6 hours, respectively.
[0790] FIGS. 3A and 3B show HaCaT cellular uptake of select peptides for 1 hour and 6 hours, respectively.
[0791] FIGS. 4A and 4B show HaCaT cellular uptake of select peptides for 1 hour and 6 hours, respectively.
[0792] FIGS. 5A and 5B show HaCaT cellular uptake of select peptides for 1 hour and 6 hours, respectively.
[0793] FIGS. 6A and 6B show HaCaT cellular uptake of select peptides for 1 hour and 6 hours, respectively.
[0794] FIG. 7 shows cellular imaging of HaCaT cell uptake of Peptide-3 after 1 hour and 6 hours, respectively.
[0795] FIG. 8 shows the release rate and amount of payload from PDC-1.
[0796] FIG. 9 shows the release rate and amount of payload from PDC-2.
[0797] FIGS. 10A and 10B show the release rate and amount of payload from PDC-48.
[0798] FIGS. 11A and 11B show the release rate and amount of payload from PDC-49.
[0799] FIGS. 12A and 12B show the release rate and amount of payload from PDC-50.
[0800] FIGS. 13A and 13B show the release rate and amount of payload from PDC-51.
[0801] FIG. 14 shows the results of stability studies of 10 Finasteride conjugates.
[0802] FIG. 15 shows the results of stability studies of Finasteride PDC-02 and Finasteride PDC-09.
[0803] FIG. 16 shows the results of payload releasing study of Finasteride PDC-02 and Finasteride PDC-09.
[0804] FIG. 17 and FIG. 18 show the results of skin penetration study of Finasteride PDC-02 and Finasteride PDC-09.
[0805] FIG. 19 shows the results of Finasteride PDCs on enzymatic inhibition towards 5α reductase.
[0806] FIG. 20 shows the cell viability of DPC cells treated with testosterone (T) at different concentrations (10 μM or 40μM) and active pharmaceutical ingredient (API) at different concentrations (75 nM, 37.5nM, 18.75 nM or 9.375nM) : finasteride (FNS) or finasteride PDC-09 (FNS PDC-09) .
[0807] FIG. 21 shows the dermal pharmacokinetic curves of finasteride PDC-09 (FNS PDC-09) and Caretopic in the skin of mini pigs.
[0808] FIG. 22 shows skin penetration study results of Sample 1.
[0809] FIG. 23 shows skin penetration study results of Sample 2. Panel A shows result of Finasteride, Panel B shows result of Finasteride PDC-09.DETAILED DESCRIPTION
[0810] The following description sets forth exemplary methods, parameters and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments.
[0811] The present disclosure is directed to peptides conjugated to a payload for the treatment of androgenetic alopecia capable of penetrating the skin and / or the cellular membranes of viable cells such as epidermal and dermal cells. Related compositions and methods are also described herein.
[0812] Definitions
[0813] Unless defined otherwise, all terms of art, notations and other technical and scientific terms or terminology used herein are intended to have the same meaning as is commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. As used herein, the singular forms "a" , "an" , and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a cell" includes a plurality of cells.
[0814] The term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, the term “about” indicates the designated value ± one standard deviation of that value. Also as used herein, "and / or" refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative ( "or" ) . Unless the context indicates otherwise, it is specifically intended that the various features of the present disclosure described herein can be used in any combination. Moreover, the present disclosure also contemplates that in some embodiments any feature or combination of features set forth herein can be excluded or omitted. To illustrate, if the specification states that a complex comprises components A, B, or C, it is specifically intended that any of A, B or C, or a combination thereof, can be omitted and disclaimed singularly or in any combination.
[0815] As used herein, by “pharmaceutically acceptable” or “cosmetically acceptable” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition or a cosmetic composition administered to a patient without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable or cosmetically acceptable carriers or excipients have in some embodiments met the required standards of toxicological and manufacturing testing and / or are included on the Inactive Ingredient Guide prepared by the U. S. Food and Drug administration.
[0816] “Pharmaceutically acceptable salts” or “cosmetically acceptable salts” are those salts which retain at least some of the biological activity of the free (non-salt) compound and which can be administered as drugs (or pharmaceuticals) or cosmetics to an individual. Such salts, for example, include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, oxalic acid, propionic acid, succinic acid, maleic acid, tartaric acid and the like; (2) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine and the like. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, and the like. Pharmaceutically acceptable salts or cosmetically acceptable salts can be prepared in situ in the manufacturing process, or by separately reacting a purified compound in its free acid or base form with a suitable organic or inorganic base or acid, respectively, and isolating the salt thus formed during subsequent purification.
[0817] The present disclosure intends to include all salts of compounds referred to herein, such as pharmaceutically acceptable salts or cosmetically acceptable salts. The present disclosure also includes any or all of the stereochemical forms, including any enantiomeric or diastereomeric forms, and any tautomers or other forms of the compounds described. Unless stereochemistry is explicitly indicated in a chemical structure or name, the structure or name is intended to embrace all possible stereoisomers of a compound depicted. In addition, where a specific stereochemical form is depicted, it is understood that other stereochemical forms are also described and embraced by the present disclosure. It is also understood that prodrugs, solvates and metabolites of the compounds are embraced by this disclosure. Compositions comprising a compound described herein are also intended, such as a composition of substantially pure compound, including a specific stereochemical form thereof. Compositions comprising a mixture of compounds described herein in any ratio are also embraced by the present disclosure, including mixtures of two or more stereochemical forms of a compound in any ratio, such that racemic, non-racemic, enantioenriched and scalemic mixtures of a compound are embraced.
[0818] The present disclosure also includes isotopically-labeled and / or isotopically-enriched forms of compounds described herein. The compounds herein may contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. In some embodiments, the compound is isotopically-labeled, where one or more atoms are replaced by an isotope of the same element. Exemplary isotopes that can be incorporated into compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine, chlorine, such as 2H, 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 34S, 35S, 18F, 36Cl, 37Cl, or 32P. Incorporation of heavier isotopes such as deuterium (2H or D) can afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life, or reduced dosage requirements, and hence may be preferred in some instances. As used herein, each instance of enrichment, substitution, or replacement of an atom with corresponding isotope of that atom encompasses isotopic enrichment levels of one of about: 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99, 6%, 99.7%, 99.8%, 99.9%, or 100%, or a range between any two of the preceding percentages.
[0819] Isotopically-labeled compounds of the present disclosure can generally be prepared by standard methods and techniques known to those skilled in the art or by procedures similar to those described in the accompanying Examples substituting appropriate isotopically-labeled reagents in place of the corresponding non-labeled reagent.
[0820] Unless clearly indicated otherwise, “an individual” or “asubject” as used herein intends a mammal, including but not limited to a primate, human, bovine, horse, feline, canine, or rodent. In one variation, the individual is a human.
[0821] As used herein, the terms “therapeutic agent” , and “therapeutic agents” refer to any agent (s) which can be used in the treatment, or prevention of a disorder, or one or more symptoms thereof. In certain embodiments, the term “therapeutic agent” includes a compound provided herein. In certain embodiments, a therapeutic agent is an agent which is known to be useful for, or has been, or is currently being used for the treatment, or prevention of a disorder, or one, or more symptoms thereof.
[0822] “Therapeutically effective amount” refers to an amount of a compound, or composition that, when administered to a subject for treating a condition, is sufficient to effect such treatment for the condition. A “therapeutically effective amount” can vary depending on, inter alia, the compound, the disease or disorder, and its severity, and the age, weight, etc., of the subject to be treated.
[0823] As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical and diagnostic results. In some embodiments, “treatment” or “treating” encompasses methods to obtain diagnostic results, such as detecting a biomarker or molecule, determining level and biodistribution of gene expression, measuring cell viability, imaging a tissue or cell, or diagnosing a disease or disorder. In some embodiments, “treatment” or “treating” encompasses methods to obtain therapeutically beneficial results, such as ameliorating the symptoms of a disease or disorder. Beneficial or desired clinical and diagnostic results include, but are not limited to, one or more of the following: detecting and diagnosing a disease or a disorder or underlying cause thereof, monitoring the development of a disease or a disorder, decreasing one more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease) , preventing or delaying the spread of the disease, delaying the occurrence or recurrence of the disease, delay or slowing the progression of the disease, ameliorating the disease state, providing a remission (whether partial or total) of the disease, decreasing the dose of one or more other medications required to treat the disease, enhancing effect of another medication, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival. The methods provided herein contemplate any one or more of these aspects of treatment.
[0824] The term “effective amount” as used herein, refers to a sufficient amount of at least one agent being administered in vitro or in vivo to achieve a desired result, e.g., to introduce or transfect a nucleic acid into a target cell, or to deliver a nucleic acid to a target organ or tissue. In certain instances, the method is in vitro, and the desired result may comprise certain desired alteration of cells or biological processes. In certain instances, the method is in vivo, and the result may comprise a delivery or transfection of a nucleic acid into a target organ or tissue, a reduction and / or alleviation of the signs, symptoms, or causes of a disease. As is understood in the art, an effective amount may be in one or more doses, i.e., a single dose or multiple doses may be required to achieve the desired treatment endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents (e.g., a compound, or pharmaceutically acceptable salt thereof) , and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable or beneficial result may be or is achieved. Suitable doses of any of the co-administered compounds may optionally be lowered due to the combined action (e.g., additive or synergistic effects) of the compounds.
[0825] In certain instances, an “effective amount” is considered in the context of therapeutical and / or diagnostic uses and may be optionally referred to as “therapeutically or pharmaceutically effective amount” . A “therapeutically effective amount” refers to an amount of the compound or the composition comprising a compound or salt thereof as set forth herein sufficient to produce a desired alteration of a target organ or tissue, or a desired therapeutic outcome and / or required to provide a clinically significant decrease in a disease. An appropriate “effective” or “therapeutically effective” amount in any individual case is determined using any suitable technique, such as a dose escalation study. In various embodiments, an effective amount or a therapeutically effective amount of the compound may (i) introduce or transfect a nucleic acid into a target cell or target cells (e.g., lung cells, spleen cells, liver cells, skeletal muscle cells, brain cells, or any combination thereof) ; (ii) deliver or transfect a nucleic acid into a target organ or target organs (e.g., lung, liver, spleen, brain, or any combination thereof) ; (iii) deliver or transfect a nucleic acid into a target tissue or target tissues (e.g., lung tissue, spleen tissue, liver tissue, skeletal muscle tissue, brain tissue, or any combination thereof) ; or (iv) alter the biological process in a cell or cells (e.g., lung cells, spleen cells, liver cells, skeletal muscle cells, brain cells, or any combination thereof) after introduction or transfection of the nucleic acid.
[0826] It is understood that embodiments of the invention described herein include “consisting of” and / or “consisting essentially of” embodiments.
[0827] The present disclosure provides peptides that are capable of penetrating the stratum corneum, epidermis, dermis and / or penetrating viable skin model cells following administration. These peptides are referred to herein as “penetrating peptides” . In some embodiments, these penetrating peptides are capable of penetrating the cellular membranes of viable epidermal and dermal cells.
[0828] The present disclosure provides skin-penetrating peptide compounds which can be useful for delivering payloads. In some embodiments, the peptide compounds can be prepared as described herein and used for therapy. In some embodiments, the therapy is a treatment of androgenetic alopecia. In some embodiments, the peptide compounds can be used to reduce hair loss or promote hair growth. In some embodiments, the peptide compounds can be used for cosmetics.
[0829] The embodiments described herein include the recited compounds as well as pharmaceutically acceptable or cosmetically acceptable salts, hydrates, solvates, isomers, and / or mixtures thereof.
[0830] In some embodiments, the skin-penetrating peptide comprises 3 to 50 amino acids, 3 to 25 amino acids, 3 to 20 amino acids, or 3 to 15 amino acids. In some embodiments, the skin-penetrating peptide comprises 3 to 50 amino acids. In some embodiments, the peptide comprises 3 to 25 amino acids. In some embodiments, the peptide comprises 3 to 20 amino acids. In some embodiments, the peptide comprises 3 to 15 amino acids. The term “N-terminal modification” as used herein, refers to a moiety capable of, covalently or otherwise, modifying the N-terminus of the aforementioned peptide. N-terminal modification is preferably selected from the group comprising acetylation, lipidation, PEGylation, cholesterol modification, polycyclic aromatic hydrocarbon modification, glycosylation, fluorination, sulfonation; preferably, acetyl modification, fatty acid modification, and pyrenebutyrate modification.
[0831] In some embodiments, the N-terminal lipidation is a branched or unbranched C6-C20 alkyl, branched or unbranched C6-C20 alkenyl, or branched or unbranched C6-C20 alkynyl. In some embodiments, the N-terminal lipidation is a branched or unbranched C9-C18 alkyl, branched or unbranched C9-C18 alkenyl, or branched or unbranched C9-C18 alkynyl. In some embodiments, the N-terminal lipidation is a branched or unbranched C9-C18 alkyl. In some embodiments, the N-terminal lipidation is an unbranched C9-C18 alkyl. In some embodiments, the N-terminal lipid is selected from the group consisting of stearyl, palmitoyl, and lauroyl. In some embodiments, the N-terminal lipid is stearyl. In some embodiments, the N-terminal lipid is palmitoyl. In some embodiments, the N-terminal lipid is lauroyl.
[0832] The term “C-terminal modification” as used herein, refers to a moiety capable of, covalently or otherwise, modifying the C-terminus of the aforementioned peptide. C-terminal modification is preferably selected from the group comprising amidation, alkylation, lipidation, PEGylation, cholesterol modification, polycyclic aromatic hydrocarbon modification; preferably, NH2.
[0833] The term “targeting moiety” as used herein, refers to an amino acid sequence in the aforementioned peptide that directs the aforementioned peptide to a specific location in a specific cell. The targeting moiety is preferably selected from the group comprising transferrin, a Penetration Accelerating Sequence (PAS) , a Nuclear Localization Signal (NLS) sequence, an Endosomal Escape Enhancer, and a Heparin Sulfate Binding Peptides; and optionally, the targeting moiety is connected to the linker, preferably by Cys or Lys residue in the targeting moiety. Preferably, the transferrin can be a sequence of Lys-His-Ala-Ile-Tyr-Pro-Arg-His. Preferably, the PAS can be a sequence of Pro-Lys-Lys-Lys-Arg-Lys-Val-βAla-Lys-Phe-Phe-Leu-Ile-Pro-Lys-Gly. Preferably, the Endosomal Escape Enhancer can be selected from the group comprising WEAALAEALAEALAEHLAEALAEALEALAA (GALA) , GLFEAIEGFIENGWEGMIDGWY (INF7) , WEAKLAKALAKALAKHLAKALAKALKACEA (KALA) , GLFHAIAHFIHGGWHGLIHGWYG (H5WYG) , and GLFGAIAGFIENGWEGMIDGWYG (HA2-Derived Peptide) . Preferably, the Heparin Sulfate Binding Peptides can be selected from the group comprising LRSRTKIIRIR (HBPep) , SPKRKGGSRKYSPTSPTTSPTSKRKYSP (HS-20) , and KHKNKRKT (Platelet Factor 4) . Preferably, the NLS sequence can be selected from the group comprising Lys -Pro-Lys-Lys-Lys-Arg-Lys-Val (NLS1) , Lys-Pro-Lys-Leu-Lys-Arg-Gln (NLS2) , Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp (NLS3) , PKKKRKV, PKLKRQ, PAAKRVKLD, RPRK, RRARRPRG, GKRKLITSEEERSPAKRGRKS, KGKKGRTQKEKKAARARSKGKN, RKRCAAGVGGGPAGCPAPGSTPLKKPRR, RKPVTAQERQREREEKRRRRQERAKEREKRRQERER, RSGGNHRRNGRGGRGGYNRRNNGYHPY, TLLLRETMNNLGVSDHAVLSRKTPQPY, PGKMDKGEHRQERRDRPY, GKKKKGKPGKRREQRKKKRRT, SANKVTKNKSNSSPYLNKRKGKPGPDS, and VHSHKKKKIPTSPTFTTPKTLTLRRQPKYPRKSAPRRNKLDHY.
[0834] In some embodiments, the peptide is selected from Table 1.
[0835] Table 1. Peptides
[0836] In some embodiments, the peptide can be further selected from:
[0837] Ac-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 47) ,
[0838] C8-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 48) ,
[0839] C10-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 49) ,
[0840] C12-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 50) ,
[0841] C14-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 51) ,
[0842] C16-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 52) ,
[0843] C18-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 53) ,
[0844] C20-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 54) ,
[0845] C22-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 55) ,
[0846] Ac-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 56) ,
[0847] C8-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 57) ,
[0848] C10-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 58) ,
[0849] C12-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 59) ,
[0850] C14-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 60) ,
[0851] C16-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 61) ,
[0852] C18-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 62) ,
[0853] C20-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 63) ,
[0854] C22-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 64) ,
[0855] Ac-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 65) ,
[0856] C8-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 66) ,
[0857] C10-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 67) ,
[0858] C12-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 68) ,
[0859] C14-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 69) ,
[0860] C16-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 70) ,
[0861] C18-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 71) ,
[0862] C20-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 72) ,
[0863] C22-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 73) ,
[0864] Ac-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 74) ,
[0865] C8-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 75) ,
[0866] C10-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 76) ,
[0867] C12-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 77) ,
[0868] C14-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 78) ,
[0869] C16-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 79) ,
[0870] C18-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 80) ,
[0871] C20-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 81) ,
[0872] C22-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 82) , Ac-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 83) ,
[0873] C8-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 84) ,
[0874] C10-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 85) ,
[0875] C12-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 86) ,
[0876] C14-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 87) ,
[0877] C16-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 88) ,
[0878] C18-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 89) ,
[0879] C20-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 90) ,
[0880] C22-Cys-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 91) ,
[0881] Ac-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 92) ,
[0882] C8-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 93) ,
[0883] C10-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 94) ,
[0884] C12-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 95) ,
[0885] C14-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 96) ,
[0886] C16-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 97) ,
[0887] C18-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 98) ,
[0888] C20-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 99) ,
[0889] C22-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-Cys-CONH2 (SEQ. ID No. 100) ;
[0890] Ac-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 101) ,
[0891] C8-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 102) ,
[0892] C10-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 103) ,
[0893] C12-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 104) ,
[0894] C14-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 105) ,
[0895] C16-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 106) ,
[0896] C18-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 107) ,
[0897] C20-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 108) ,
[0898] C22-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 109) ,
[0899] Ac-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 110) ,
[0900] C8-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 111) ,
[0901] C10-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 112) ,
[0902] C12-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 113) ,
[0903] C14-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 114) ,
[0904] C16-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 115) ,
[0905] C18-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 116) ,
[0906] C20-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 117) ,
[0907] C22-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 118) ,
[0908] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 119) (NLS1-Arg-(βAla-Arg) 5) ,
[0909] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 120) (NLS1-Arg-(βAla-Arg) 5) ,
[0910] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 121) (NLS1-Arg-(βAla-Arg) 5) ,
[0911] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 122) (NLS1-Arg-(βAla-Arg) 5) ,
[0912] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 123) (NLS1-Arg-(βAla-Arg) 5) ,
[0913] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 124) (NLS1-Arg-(βAla-Arg) 5) ,
[0914] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 125) (NLS1-Arg-(βAla-Arg) 5) ,
[0915] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 126) (NLS1-Arg- (βAla-Arg) 5) ,
[0916] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 127) (NLS1-Arg- (βAla-Arg) 5) ,
[0917] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 128) (NLS1-Arg- (βAla-Arg) 5) ,
[0918] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 129) (NLS1-Arg- (βAla-Arg) 5) ,
[0919] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 130) (NLS1-Arg- (βAla-Arg) 5) ,
[0920] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 131) (NLS1-Arg- (βAla-Arg) 5) ,
[0921] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 132) (NLS1-Arg- (βAla-Arg) 5) ,
[0922] C16-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 133) (NLS1-Arg- (βAla-Arg) 5) ,
[0923] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 134) (NLS1-Arg- (βAla-Arg) 5) ,
[0924] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 135) (NLS1-Arg- (βAla-Arg) 5) ,
[0925] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-CONH2, (SEQ. ID No. 136) (NLS1-Arg- (βAla-Arg) 5) ,
[0926] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 137) (NLS1-Arg- (βAla-Arg) 4) ,
[0927] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 138) (NLS1-Arg- (βAla-Arg) 4) ,
[0928] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 139) (NLS1-Arg- (βAla-Arg) 4) ,
[0929] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 140) (NLS1-Arg- (βAla-Arg) 4) ,
[0930] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 141) (NLS1-Arg- (βAla-Arg) 4) ,
[0931] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 142) (NLS1-Arg- (βAla-Arg) 4) ,
[0932] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 143) (NLS1-Arg- (βAla-Arg) 4) ,
[0933] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 144) (NLS1-Arg- (βAla-Arg) 4) ,
[0934] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 145) (NLS1-Arg- (βAla-Arg) 4) ,
[0935] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 146) (NLS1-Arg- (βAla-Arg) 4) ,
[0936] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 147) (NLS1-Arg- (βAla-Arg) 4) ,
[0937] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 148) (NLS1-Arg- (βAla-Arg) 4) ,
[0938] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 149) (NLS1-Arg- (βAla-Arg) 4) ,
[0939] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 150) (NLS1-Arg- (βAla-Arg) 4) ,
[0940] C16-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 151) (NLS1-Arg- (βAla-Arg) 4) ,
[0941] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 152) (NLS1-Arg- (βAla-Arg) 4) ,
[0942] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 153) (NLS1-Arg- (βAla-Arg) 4) ,
[0943] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 154) (NLS1-Arg- (βAla-Arg) 4) ,
[0944] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 155) (NLS2-Arg- (βAla-Arg) 4) ,
[0945] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 156) (NLS2-Arg- (βAla-Arg) 4) ,
[0946] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 157) (NLS2-Arg- (βAla-Arg) 4) ,
[0947] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 158) (NLS2-Arg- (βAla-Arg) 4) ,
[0948] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 159) (NLS2-Arg- (βAla-Arg) 4) ,
[0949] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 160) (NLS2-Arg- (βAla-Arg) 4) ,
[0950] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 161) (NLS2-Arg- (βAla-Arg) 4) ,
[0951] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 162) (NLS2-Arg- (βAla-Arg) 4) ,
[0952] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 163) (NLS2-Arg- (βAla-Arg) 4) ,
[0953] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 164) (NLS2-Arg- (βAla-Arg) 4) ,
[0954] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 165) (NLS2-Arg- (βAla-Arg) 4) ,
[0955] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 166) (NLS2-Arg- (βAla-Arg) 4) ,
[0956] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 167) (NLS2-Arg- (βAla-Arg) 4) ,
[0957] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 168) (NLS2-Arg- (βAla-Arg) 4) ,
[0958] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 169) (NLS2-Arg- (βAla-Arg) 4) ,
[0959] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 170) (NLS2-Arg- (βAla-Arg) 4) ,
[0960] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 171) (NLS2-Arg- (βAla-Arg) 4) ,
[0961] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 172) (NLS2-Arg- (βAla-Arg) 4) ,
[0962] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 173) (NLS3-Arg- (βAla-Arg) 4) ,
[0963] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 174) (NLS3-Arg- (βAla-Arg) 4) ,
[0964] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 175) (NLS3-Arg- (βAla-Arg) 4) ,
[0965] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 176) (NLS3-Arg- (βAla-Arg) 4) ,
[0966] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 177) (NLS3-Arg- (βAla-Arg) 4) ,
[0967] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 178) (NLS3-Arg- (βAla-Arg) 4) ,
[0968] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 179) (NLS3-Arg- (βAla-Arg) 4) ,
[0969] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 180) (NLS3-Arg- (βAla-Arg) 4) ,
[0970] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 181) (NLS3-Arg- (βAla-Arg) 4) ,
[0971] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 182) (NLS3-Arg- (βAla-Arg) 4) ,
[0972] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 183) (NLS3-Arg- (βAla-Arg) 4) ,
[0973] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 184) (NLS3-Arg- (βAla-Arg) 4) ,
[0974] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 185) (NLS3-Arg- (βAla-Arg) 4) ,
[0975] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 186) (NLS3-Arg- (βAla-Arg) 4) ,
[0976] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 187) (NLS3-Arg- (βAla-Arg) 4) ,
[0977] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 188) (NLS3-Arg- (βAla-Arg) 4) ,
[0978] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 189) (NLS3-Arg- (βAla-Arg) 4) ,
[0979] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-CONH2, (SEQ. ID No. 190) (NLS3-Arg- (βAla-Arg) 4) ,
[0980] Ac-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 191) ,
[0981] C8-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 192) ,
[0982] C10-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 193) ,
[0983] C12-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 194) ,
[0984] C14-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 195) ,
[0985] C16-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 196) ,
[0986] C18-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 197) ,
[0987] C20-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 198) ,
[0988] C22-Cys-Arg- (βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 199) ,
[0989] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 200) (NLS1-Arg- (βAla-Arg) 5)
[0990] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 201) (NLS1-Arg- (βAla-Arg) 5)
[0991] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 202) (NLS1-Arg- (βAla-Arg) 5)
[0992] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 203) (NLS1-Arg- (βAla-Arg) 5)
[0993] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 204) (NLS1-Arg- (βAla-Arg) 5)
[0994] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 205) (NLS1-Arg- (βAla-Arg) 5)
[0995] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 206) (NLS1-Arg- (βAla-Arg) 5)
[0996] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 207) (NLS1-Arg- (βAla-Arg) 5)
[0997] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 5-Cys-CONH2, (SEQ. ID No. 208) (NLS1-Arg- (βAla-Arg) 5)
[0998] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 209) (NLS1-Arg- (βAla-Arg) 4) ,
[0999] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 210) (NLS1-Arg- (βAla-Arg) 4) ,
[1000] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 211) (NLS1-Arg- (βAla-Arg) 4) ,
[1001] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 212) (NLS1-Arg- (βAla-Arg) 4) ,
[1002] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 213) (NLS1-Arg- (βAla-Arg) 4) ,
[1003] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 214) (NLS1-Arg- (βAla-Arg) 4) ,
[1004] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 215) (NLS1-Arg- (βAla-Arg) 4) ,
[1005] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 216) (NLS1-Arg- (βAla-Arg) 4) ,
[1006] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 217) (NLS1-Arg- (βAla-Arg) 4) ,
[1007] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 218) (NLS2-Arg-(βAla-Arg) 4) ,
[1008] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 219) (NLS2-Arg-(βAla-Arg) 4) ,
[1009] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 220) (NLS2-Arg-(βAla-Arg) 4) ,
[1010] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 221) (NLS2-Arg-(βAla-Arg) 4) ,
[1011] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 222) (NLS2-Arg-(βAla-Arg) 4) ,
[1012] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 223) (NLS2-Arg-(βAla-Arg) 4) ,
[1013] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 224) (NLS2-Arg-(βAla-Arg) 4) ,
[1014] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 225) (NLS2-Arg-(βAla-Arg) 4) ,
[1015] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 226) (NLS2-Arg-(βAla-Arg) 4) ,
[1016] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 227) (NLS3-Arg- (βAla-Arg) 4) ,
[1017] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 228) (NLS3-Arg- (βAla-Arg) 4) ,
[1018] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 229) (NLS3-Arg- (βAla-Arg) 4) ,
[1019] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 230) (NLS3-Arg- (βAla-Arg) 4) ,
[1020] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 231) (NLS3-Arg- (βAla-Arg) 4) ,
[1021] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 232) (NLS3-Arg- (βAla-Arg) 4) ,
[1022] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 233) (NLS3-Arg- (βAla-Arg) 4) ,
[1023] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 234) (NLS3-Arg- (βAla-Arg) 4) ,
[1024] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp-Arg- (βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 235) (NLS3-Arg- (βAla-Arg) 4) ,
[1025] Acetyl- (GuanidylC6NHPeptoid-Ahx) 7GuanidylC6NHPeptoid-Cys-NH2, (SEQ. ID No. 236)
[1026] C18-Ahx-GuanidylC6NHPeptoid- (Ahx-GuanidylC6NHPeptoid) 7-Cys-NH2 (SEQ. ID No. 237) ;
[1027] Ac- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 238) ,
[1028] C8- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 239) ,
[1029] C10- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 240) ,
[1030] C12- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 241) ,
[1031] C14- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 242) ,
[1032] C16- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 243) ,
[1033] C18- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 244) ,
[1034] C20- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 245) ,
[1035] C22- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 246) ,
[1036] Ac- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 247) ,
[1037] C8- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 248) ,
[1038] C10- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 249) ,
[1039] C12- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 250) ,
[1040] C14- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 251) ,
[1041] C16- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 252) ,
[1042] C18- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 253) ,
[1043] C20- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 254) ,
[1044] C22- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 255) ,
[1045] Ac- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 256) ,
[1046] C8- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 257) ,
[1047] C10- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 258) ,
[1048] C12- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 259) ,
[1049] C14- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 260) ,
[1050] C16- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 261) ,
[1051] C18- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 262) ,
[1052] C20- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 263) ,
[1053] C22- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 264) ,
[1054] Ac- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 265) ,
[1055] C8- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 266) ,
[1056] C10- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 267) ,
[1057] C12- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 268) ,
[1058] C14- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 269) ,
[1059] C16- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 270) ,
[1060] C18- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 271) ,
[1061] C20- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 272) ,
[1062] C22- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 273) ,
[1063] Ac-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 274) ,
[1064] C8-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 275) ,
[1065] C10-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 276) ,
[1066] C12-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 277) ,
[1067] C14-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 278) ,
[1068] C16-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 279) ,
[1069] C18-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 280) ,
[1070] C20-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 281) ,
[1071] C22-Cys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 282) ,
[1072] Ac-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 283) ,
[1073] C8-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 284) ,
[1074] C10-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 285) ,
[1075] C12-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 286) ,
[1076] C14-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 287) ,
[1077] C16-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 288) ,
[1078] C18-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 289) ,
[1079] C20-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 290) ,
[1080] C22-Lys- (Arg-βAla-Arg) 4-CONH2 (SEQ. ID No. 291) ,
[1081] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 292) (NLS1- (Arg-βAla-Arg) 4) ,
[1082] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 293) (NLS1- (Arg-βAla-Arg) 4) ,
[1083] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 294) (NLS1- (Arg-βAla-Arg) 4) ,
[1084] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 295) (NLS1- (Arg-βAla-Arg) 4) ,
[1085] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 296) (NLS1- (Arg-βAla-Arg) 4) ,
[1086] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 297) (NLS1- (Arg-βAla-Arg) 4) ,
[1087] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 298) (NLS1- (Arg-βAla-Arg) 4) ,
[1088] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 299) (NLS1- (Arg-βAla-Arg) 4) ,
[1089] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 300) (NLS1- (Arg-βAla-Arg) 4) ,
[1090] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 301) (NLS1- (Arg-βAla-Arg) 4) ,
[1091] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 302) (NLS1- (Arg-βAla-Arg) 4) ,
[1092] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 303) (NLS1- (Arg-βAla-Arg) 4) ,
[1093] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 304) (NLS1- (Arg-βAla-Arg) 4) ,
[1094] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 305) (NLS1- (Arg-βAla-Arg) 4) ,
[1095] C16-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 306) (NLS1- (Arg-βAla-Arg) 4) ,
[1096] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 307) (NLS1- (Arg-βAla-Arg) 4) ,
[1097] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 308) (NLS1- (Arg-βAla-Arg) 4) ,
[1098] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-CONH2, (SEQ. ID No. 309) (NLS1- (Arg-βAla-Arg) 4) ,
[1099] Ac-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 310) ,
[1100] C8-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 311) ,
[1101] C10-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 312) ,
[1102] C12-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 313) ,
[1103] C14-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 314) ,
[1104] C16-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 315) ,
[1105] C18-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 316) ,
[1106] C20-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 317) ,
[1107] C22-Cys- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 318) ,
[1108] Ac-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 319) ,
[1109] C8-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 320) ,
[1110] C10-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 321) ,
[1111] C12-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 322
[1112] C14-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 323) ,
[1113] C16-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 324) ,
[1114] C18-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 325) ,
[1115] C20-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 326) ,
[1116] C22-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 327
[1117] Ac-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 328) ,
[1118] C8-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 329) ,
[1119] C10-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 330) ,
[1120] C12-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 331
[1121] C14-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 332) ,
[1122] C16-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 333) ,
[1123] C18-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 334) ,
[1124] C20-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 335) ,
[1125] C22-Cys- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 336) ,
[1126] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 337) (NLS1- (Arg-βAla-Arg) 4) ,
[1127] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 338) (NLS1- (Arg-βAla-Arg) 4) ,
[1128] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 339) (NLS1- (Arg-βAla-Arg) 4) ,
[1129] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 340) (NLS1- (Arg-βAla-Arg) 4) ,
[1130] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 341) (NLS1- (Arg-βAla-Arg) 4) ,
[1131] C16-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 342) (NLS1- (Arg-βAla-Arg) 4) ,
[1132] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 343) (NLS1- (Arg-βAla-Arg) 4) ,
[1133] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 344) (NLS1- (Arg-βAla-Arg) 4) ,
[1134] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (Arg-βAla-Arg) 4-Cys-CONH2, (SEQ. ID No. 345) (NLS1- (Arg-βAla-Arg) 4) ;
[1135] Ac-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 346) ,
[1136] C8-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 347) ,
[1137] C10-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 348) ,
[1138] C12-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 349) ,
[1139] C14-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 350) ,
[1140] C16-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 351) ,
[1141] C18-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 352) ,
[1142] C20-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 353) ,
[1143] C22-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 354) ,
[1144] Ac-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 355) ,
[1145] C8-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 356) ,
[1146] C10-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 357) ,
[1147] C12-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 358) ,
[1148] C14-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 359) ,
[1149] C16-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 360) ,
[1150] C18-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 361) ,
[1151] C20-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 362) ,
[1152] C22-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 363) ,
[1153] Ac-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 364) ,
[1154] C8-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 365) ,
[1155] C10-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 366) ,
[1156] C12-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 367) ,
[1157] C14-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 368) ,
[1158] C16-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 369) ,
[1159] C18-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 370) ,
[1160] C20-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 371) ,
[1161] C22-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 372) ,
[1162] Ac-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 373) ,
[1163] C8-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 374) ,
[1164] C10-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 375) ,
[1165] C12-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 376) ,
[1166] C14-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 377) ,
[1167] C16-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 378) ,
[1168] C18-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 379) ,
[1169] C20-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 380) ,
[1170] C22-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 381) ,
[1171] Ac-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 382) ,
[1172] C8-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 383) ,
[1173] C10-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 384) ,
[1174] C12-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 385) ,
[1175] C14-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 386) ,
[1176] C16-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 387) ,
[1177] C18-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 388) ,
[1178] C20-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 389) ,
[1179] C22-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 390) ,
[1180] Ac-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 391) ,
[1181] C8-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 392) ,
[1182] C10-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 393) ,
[1183] C12-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 394) ,
[1184] C14-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 395) ,
[1185] C16-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 396) ,
[1186] C18-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 397) ,
[1187] C20-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 398) ,
[1188] C22-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 399) ,
[1189] Ac-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 400) ,
[1190] C8-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 401) ,
[1191] C10-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 402) ,
[1192] C12-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 403) ,
[1193] C14-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 404) ,
[1194] C16-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 405) ,
[1195] C18-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 406) ,
[1196] C20-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 407) ,
[1197] C22-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 408) ,
[1198] Ac-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 409) ,
[1199] C8-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 410) ,
[1200] C10-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 411) ,
[1201] C12-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 412) ,
[1202] C14-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 413) ,
[1203] C16-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 414) ,
[1204] C18-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 415) ,
[1205] C20-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 416) ,
[1206] C22-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 417) ,
[1207] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 418) (NLS1-pRR3) , C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 419) (NLS1-pRR3) ,
[1208] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 420) (NLS1-pRR3) ,
[1209] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 421) (NLS1-pRR3) ,
[1210] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 422) (NLS1-pRR3) ,
[1211] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 423) (NLS1-pRR3) ,
[1212] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 424 (NLS1-pRR3) ,
[1213] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 425) (NLS1-pRR3) ,
[1214] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 426) (NLS1-pRR3) ,
[1215] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 427) (NLS1-pRR3) ,
[1216] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 428) (NLS1-pRR3) ,
[1217] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 429) (NLS1-pRR3) ,
[1218] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 430) (NLS1-pRR3) ,
[1219] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 431) (NLS1-pRR3) ,
[1220] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 432) (NLS1-pRR3) ,
[1221] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 433) (NLS1-pRR3) ,
[1222] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 434) (NLS2-pRR3) ,
[1223] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 435) (NLS2-pRR3) ,
[1224] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 436) (NLS2-pRR3) ,
[1225] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 437) (NLS2-pRR3) ,
[1226] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 438) (NLS2-pRR3) ,
[1227] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 439) (NLS2-pRR3) ,
[1228] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 440) (NLS2-pRR3) ,
[1229] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 441) (NLS2-pRR3) ,
[1230] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 442) (NLS2-pRR3) ,
[1231] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 443) (NLS2-pRR3) ,
[1232] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 444) (NLS2-pRR3) ,
[1233] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 445) (NLS2-pRR3) ,
[1234] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 446) (NLS2-pRR3) ,
[1235] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 447) (NLS2-pRR3) ,
[1236] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 448) (NLS2-pRR3) ,
[1237] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 449) (NLS2-pRR3) ,
[1238] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 450) (NLS2-pRR3) ,
[1239] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 451) (NLS2-pRR3) ,
[1240] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 452) (NLS3-pRR3) ,
[1241] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 453) (NLS3-pRR3) ,
[1242] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 454) (NLS3-pRR3) ,
[1243] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 455) (NLS3-pRR3) ,
[1244] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 456) (NLS3-pRR3) ,
[1245] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 457) (NLS3-pRR3) ,
[1246] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 458) (NLS3-pRR3) ,
[1247] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 459) (NLS3-pRR3) ,
[1248] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 460) (NLS3-pRR3) ,
[1249] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 461) (NLS3-pRR3) ,
[1250] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 462) (NLS3-pRR3) ,
[1251] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 463) (NLS3-pRR3) ,
[1252] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 464) (NLS3-pRR3) ,
[1253] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 465) (NLS3-pRR3) ,
[1254] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 466) (NLS3-pRR3) ,
[1255] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 467) (NLS3-pRR3) ,
[1256] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 468) (NLS3-pRR3) ,
[1257] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 469) (NLS3-pRR3) ,
[1258] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 470) (NLS1-pRR4) ,
[1259] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 471) (NLS1-pRR4) ,
[1260] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 472) (NLS1-pRR4) ,
[1261] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 473) (NLS1-pRR4) ,
[1262] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 474) (NLS1-pRR4) ,
[1263] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 475) (NLS1-pRR4) ,
[1264] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 476) (NLS1-pRR4) ,
[1265] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 477) (NLS1-pRR4) ,
[1266] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 478) (NLS1-pRR4) ,
[1267] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 479) (NLS1-pRR4) ,
[1268] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 480) (NLS1-pRR4) ,
[1269] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 481) (NLS1-pRR4) ,
[1270] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 482) (NLS1-pRR4) ,
[1271] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 483) (NLS1-pRR4) ,
[1272] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 484) (NLS1-pRR4) ,
[1273] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 485) (NLS1-pRR4) ,
[1274] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 486) (NLS2-pRR4) ,
[1275] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 487) (NLS2-pRR4) ,
[1276] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 488) (NLS2-pRR4) ,
[1277] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 489) (NLS2-pRR4) ,
[1278] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 490) (NLS2-pRR4) ,
[1279] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 491) (NLS2-pRR4) ,
[1280] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 492) (NLS2-pRR4) ,
[1281] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 493) (NLS2-pRR4) ,
[1282] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 494) (NLS2-pRR4) ,
[1283] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 495) (NLS2-pRR4) ,
[1284] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 496) (NLS2-pRR4) ,
[1285] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 497) (NLS2-pRR4) ,
[1286] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 498) (NLS2-pRR4) ,
[1287] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 499) (NLS2-pRR4) ,
[1288] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 500) (NLS2-pRR4) ,
[1289] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 501) (NLS2-pRR4) ,
[1290] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 502) (NLS2-pRR4) ,
[1291] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 503) (NLS2-pRR4) ,
[1292] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 504) (NLS3-pRR4) ,
[1293] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 505) (NLS3-pRR4) ,
[1294] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 506) (NLS3-pRR4) ,
[1295] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 507) (NLS3-pRR4) ,
[1296] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 508) (NLS3-pRR4) ,
[1297] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 509) (NLS3-pRR4) ,
[1298] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 510) (NLS3-pRR4) ,
[1299] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 511) (NLS3-pRR4) ,
[1300] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 512) (NLS3-pRR4) ,
[1301] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 513) (NLS3-pRR4) ,
[1302] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 514) (NLS3-pRR4) ,
[1303] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 515) (NLS3-pRR4) ,
[1304] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 516) (NLS3-pRR4) ,
[1305] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 517) (NLS3-pRR4) ,
[1306] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 518) (NLS3-pRR4) ,
[1307] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 519) (NLS3-pRR4) ,
[1308] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 520) (NLS3-pRR4) ,
[1309] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 521) (NLS3-pRR4) ,
[1310] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 522) (NLS1-pRR5) ,
[1311] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 523) (NLS1-pRR5) ,
[1312] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 524) (NLS1-pRR5) ,
[1313] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 525) (NLS1-pRR5) ,
[1314] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 526) (NLS1-pRR5) ,
[1315] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 527) (NLS1-pRR5) ,
[1316] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 528) (NLS1-pRR5) ,
[1317] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 529) (NLS1-pRR5) ,
[1318] Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 530) (NLS1-pRR5) ,
[1319] C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 531) (NLS1-pRR5) ,
[1320] C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 532) (NLS1-pRR5) ,
[1321] C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 533) (NLS1-pRR5) ,
[1322] C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 534) (NLS1-pRR5) ,
[1323] C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 535) (NLS1-pRR5) ,
[1324] C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 536) (NLS1-pRR5) ,
[1325] C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 537) (NLS1-pRR5) ,
[1326] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 538) (NLS2-pRR5) ,
[1327] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 539) ,
[1328] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 540) ,
[1329] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 541) ,
[1330] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 542) ,
[1331] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 543) ,
[1332] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 544) ,
[1333] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 545) ,
[1334] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 546) ,
[1335] Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 547) (NLS2-pRR5) ,
[1336] C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 548) (NLS2-pRR5) ,
[1337] C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 549) (NLS2-pRR5) ,
[1338] C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 550) (NLS2-pRR5) ,
[1339] C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 551) (NLS2-pRR5) ,
[1340] C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 552) (NLS2-pRR5) ,
[1341] C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 553) (NLS2-pRR5) ,
[1342] C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 554) (NLS2-pRR5) ,
[1343] C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 555) (NLS2-pRR5) ,
[1344] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 556) (NLS3-pRR5) ,
[1345] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 557) (NLS3-pRR5) ,
[1346] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 558) (NLS3-pRR5) ,
[1347] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 559) (NLS3-pRR5) ,
[1348] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 560) (NLS3-pRR5) ,
[1349] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 561) (NLS3-pRR5) ,
[1350] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 562) (NLS3-pRR5) ,
[1351] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 563) (NLS3-pRR5) ,
[1352] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 564) (NLS3-pRR5) ,
[1353] Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 565) (NLS3-pRR5) ,
[1354] C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 566) (NLS3-pRR5) ,
[1355] C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 567) (NLS3-pRR5) ,
[1356] C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 568) (NLS3-pRR5) ,
[1357] C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 569) (NLS3-pRR5) ,
[1358] C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 570) (NLS3-pRR5) ,
[1359] C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 571) (NLS3-pRR5) ,
[1360] C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 572) (NLS3-pRR5) ,
[1361] C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 573) (NLS3-pRR5) ,
[1362] Ac-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 574) ,
[1363] C8-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 575) ,
[1364] C10-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 576) ,
[1365] C12-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 577) ,
[1366] C14-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 578) ,
[1367] C16-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 579) ,
[1368] C18-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 580) ,
[1369] C20-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 581) ,
[1370] C22-Cys- (DPro-Arg-D-Arg) 3-Cys-COOH, (SEQ. ID No. 582) ,
[1371] Ac-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 583) ,
[1372] C8-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 584) ,
[1373] C10-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 585) ,
[1374] C12-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 586) ,
[1375] C14-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 587) ,
[1376] C16-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 588) ,
[1377] C18-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 589) ,
[1378] C20-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 590) ,
[1379] C22-Cys- (DPro-Arg-Arg) 5-Cys-COOH, (SEQ. ID No. 591) ,
[1380] Ac-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 592) ,
[1381] C8-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 593) ,
[1382] C10-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 594) ,
[1383] C12-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 595) ,
[1384] C14-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 596) ,
[1385] C16-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 597) ,
[1386] C18-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 598) ,
[1387] C20-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 599) ,
[1388] C22-Cys- (DPro-Arg-Arg) 4-Cys-COOH, (SEQ. ID No. 600) ,
[1389] Ac-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 601) ,
[1390] C8-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 602) ,
[1391] C10-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 603) ,
[1392] C12-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 604) ,
[1393] C14-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 605) ,
[1394] C16-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 606) ,
[1395] C18-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 607) ,
[1396] C20-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 608) ,
[1397] C22-Cys- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 609) ,
[1398] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 610) (NLS1-pRR3) ,
[1399] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 611) (NLS1-pRR3) ,
[1400] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 612) (NLS1-pRR3) ,
[1401] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 613) (NLS1-pRR3) ,
[1402] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 614) (NLS1-pRR3) ,
[1403] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 615) (NLS1-pRR3) ,
[1404] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 616) (NLS1-pRR3) ,
[1405] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 617) (NLS1-pRR3) ,
[1406] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 618) (NLS2-pRR3) ,
[1407] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 619) (NLS2-pRR3) ,
[1408] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 620) (NLS2-pRR3) ,
[1409] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 621) (NLS2-pRR3) ,
[1410] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 622) (NLS2-pRR3) ,
[1411] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 623) (NLS2-pRR3) ,
[1412] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 624) (NLS2-pRR3) ,
[1413] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 625) (NLS2-pRR3) ,
[1414] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 626) (NLS2-pRR3) ,
[1415] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 627) (NLS3-pRR3) ,
[1416] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 628) (NLS3-pRR3) ,
[1417] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 629) (NLS3-pRR3) ,
[1418] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 630) (NLS3-pRR3) ,
[1419] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 631) (NLS3-pRR3) ,
[1420] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 632) (NLS3-pRR3) ,
[1421] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 633) (NLS3-pRR3) ,
[1422] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 634) (NLS3-pRR3) ,
[1423] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-Cys-CONH2, (SEQ. ID No. 635) (NLS3-pRR3) ,
[1424] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 636) (NLS1-pRR4) ,
[1425] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 637) (NLS1-pRR4) ,
[1426] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 638) (NLS1-pRR4) ,
[1427] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 639) (NLS1-pRR4) ,
[1428] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 640) (NLS1-pRR4) ,
[1429] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 641) (NLS1-pRR4) ,
[1430] C20-CysPro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 642) (NLS1-pRR4) ,
[1431] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 643) (NLS1-pRR4) ,
[1432] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 644) (NLS2-pRR4) ,
[1433] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 645) (NLS2-pRR4) ,
[1434] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 646) (NLS2-pRR4) ,
[1435] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 647) (NLS2-pRR4) ,
[1436] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 648) (NLS2-pRR4) ,
[1437] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 649) (NLS2-pRR4) ,
[1438] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 650) (NLS2-pRR4) ,
[1439] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 651) (NLS2-pRR4) ,
[1440] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 652) (NLS2-pRR4) ,
[1441] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 653) (NLS3-pRR4) ,
[1442] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 654) (NLS3-pRR4) ,
[1443] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 655) (NLS3-pRR4) ,
[1444] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 656) (NLS3-pRR4) ,
[1445] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 657) (NLS3-pRR4) ,
[1446] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 658) (NLS3-pRR4) ,
[1447] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 659) (NLS3-pRR4) ,
[1448] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 660) (NLS3-pRR4) ,
[1449] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-Cys-CONH2, (SEQ. ID No. 661) (NLS3-pRR4) ,
[1450] Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 662) (NLS1-pRR5) ,
[1451] C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 663) (NLS1-pRR5) ,
[1452] C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 664) (NLS1-pRR5) ,
[1453] C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 665) (NLS1-pRR5) ,
[1454] C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 666) (NLS1-pRR5) ,
[1455] C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 667) (NLS1-pRR5) ,
[1456] C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 668) (NLS1-pRR5) ,
[1457] C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 669) (NLS1-pRR5) ,
[1458] Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 670) (NLS2-pRR5) ,
[1459] C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 671) (NLS2-pRR5) ,
[1460] C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 672) (NLS2-pRR5) ,
[1461] C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 673) (NLS2-pRR5) ,
[1462] C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 674) (NLS2-pRR5) ,
[1463] C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 675) (NLS2-pRR5) ,
[1464] C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 676) (NLS2-pRR5) ,
[1465] C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 677) (NLS2-pRR5) ,
[1466] C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 678) (NLS2-pRR5) ,
[1467] Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 679) (NLS3-pRR5) ,
[1468] C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 680) (NLS3-pRR5) ,
[1469] C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 681) (NLS3-pRR5) ,
[1470] C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 682) (NLS3-pRR5) ,
[1471] C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 683) (NLS3-pRR5) ,
[1472] C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 684) (NLS3-pRR5) ,
[1473] C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 685) (NLS3-pRR5) ,
[1474] C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 686) (NLS3-pRR5) ,
[1475] C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-Cys-CONH2, (SEQ. ID No. 687) (NLS3-pRR5) ;
[1476] C18-Cys-Arg-Arg-Trp-Trp-Arg-Arg-Trp-Arg-Arg-CONH2 (SEQ. ID No. 688) .
[1477] In some embodiments, the peptide can be replaced by peptoids. Examples of peptoids can be as follows:
[1478] The present disclosure provides skin-penetrating peptide-drug conjugates (PDC) useful for delivering payloads. In certain embodiments, the PDCs can be prepared as described herein and used for therapy. The PDC comprises a peptide and a payload, with the peptide covalently binds to the payload via a linker.
[1479] Peptides
[1480] The present disclosure provides peptides as described in the previous section.
[1481] Linkers
[1482] Types of Linkers
[1483] In some embodiments, the conjugate comprises a payload covalently bound to a peptide via a linker. In some embodiments, the linker comprises an alkyl, an amide, an ester, a disulfide, a sulfide, a ketal, a succinate, an oxime, a carbamate, an ether, an aryl, a heteroaryl, a cyclyl, or a heterocyclyl. In some embodiments, the linker comprises an alkyl, an amide, or an ester. In some embodiments, the linker comprises an alkyl. In some embodiments, the linker comprises an amide. In some embodiments, the linker comprises an ester. In some embodiments, the linker is a cleavable or non-cleavable linker. In some embodiments, the linker is a cleavable linker. In some embodiments, the linker is a non-cleavable linker. In some embodiments, the linker comprises C1-C20 alkyl. In some embodiments, the linker comprises C2-C10 alkyl. In some embodiments, the linker comprises C2-C6 alkyl. In some embodiments, the linker is branched or linear. In some embodiments, the linker is branched. In some embodiments, the linker is linear. In some embodiments, the linker is a peptide-based linker. In some embodiments, the linker is not a peptide-based linker. In some embodiments, the linker covalently binds multiple payloads to one peptide. In some embodiments, the linker covalently binds two payloads to one peptide. In some embodiments, the linker covalently binds one payload to one peptide.
[1484] Linker Species
[1485] In some embodiments, the linker is selected from:
[1486] wherein t is an integer of from 1 to 10. In some embodiments, t is an integer of from 1 to 5.
[1487] Preferably, wherein are preferably for cysteine conjugation, and is preferably for lysine conjugation.
[1488] In some embodiments, t is an integer of from 1 to 3. In some embodiments, the linker is selected from .In some embodiments, the linker is selected from where t is an integer from 1 to 3. In some embodiments, the linker is selected from , where t is an integer from 1 to 3. In some embodiments, the linker is selected from , where t is an integer from 1 to 3. In some embodiments, the linker is selected from the group consisting of .In some embodiments, the linker is . In some embodiments, the linker is . In some embodiments, the linker is In some embodiments, the linker is . In some embodiments, the linker is
[1489] Payload
[1490] In some embodiments, the payload is used to treat androgenetic alopecia. In some embodiments, the payload is used to reduce hair loss or promote hair growth. In some embodiments, the payload is selected from finasteride, minoxidil, dutasteride, spironolactone, flutamide, bicalutamide, cyproterone acetate, ketaconazole, and prostaglandin F2 analogues. In some embodiments, the payload is selected from the group consisting of finasteride, minoxidil, dutasteride, spironolactone, flutamide, and ketaconazole. In some embodiments, the payload is selected from the group consisting of finasteride, minoxidil, and dutasteride. In some embodiments, the payload is finasteride. In some embodiments, the payload is minoxidil. In some embodiments, the payload is dutasteride.
[1491] In some embodiments, the payload is used for cosmetics. In some embodiments, the payload is used for hair care. In some embodiments, the payload is used to reduce hair loss or promote hair growth. In some embodiments, the payload is selected from finasteride, minoxidil, dutasteride, spironolactone, flutamide, bicalutamide, cyproterone acetate, ketaconazole, and prostaglandin F2 analogues. In some embodiments, the payload is selected from the group consisting of finasteride, minoxidil, dutasteride, spironolactone, flutamide, and ketaconazole. In some embodiments, the payload is selected from the group consisting of finasteride, minoxidil, and dutasteride. In some embodiments, the payload is finasteride. In some embodiments, the payload is minoxidil. In some embodiments, the payload is dutasteride.
[1492] In some preferable embodiments, the payload is a therapeutic agent, and is preferably an agent for the treatment of androgenetic alopecia; and more preferably the payload is selected from the group comprising finasteride, minoxidil, and dutasteride, including all the stereisomer of these compounds. The exemplary chemical structures of finasteride, minoxidil and dutasteride can be, for example, as follows:
[1493] Finasteride:
[1494] Minoxidil:
[1495] Dutasteride:
[1496] In some embodiments, the PDC is selected from Table 2.
[1497] Table 2. Peptide-drug conjugates (PDCs)
[1498] In some embodiments, the PDC can be further selected from the following lists:
[1499] Finasteride PDCs -Linker 1
[1500] Finasteride PDCs -Linker 2
[1501] Finasteride PDCs -Linker 3
[1502] Finasteride PDCs -Linker 4
[1503] Finasteride PDCs -Linker 5
[1504] Finasteride PDCs-Linker 1-2payload
[1505] Minoxidil-PDCs-Linker1
[1506] Minoxidil-PDCs-Linker2
[1507] Minoxidil-PDCs-Linker1-2Peptide
[1508] Minoxidil-PDCs-Linker2-2Peptide
[1509] In some embodiments, the PDC of the present application can successfully release the payload resulting in about 30 to 100%release. In some embodiments, the PDC can successfully release the payload resulting in about 40 to 90%release. In some embodiments, the PDC can successfully release the payload resulting in about 50 to 80%release. In some embodiments, the PDC can successfully release the payload resulting in about 60 to 70%release. In some embodiments, the PDC can successfully release the payload resulting in about 30 to 90%release. In some embodiments, the PDC can successfully release the payload resulting in about 30 to 80%release. In some embodiments, the PDC can successfully release the payload resulting in about 30 to 70%release. In some embodiments, the PDC can successfully release the payload resulting in about 30 to 60%release. In some embodiments, the PDC can successfully release the payload resulting in about 50 to 100%release. In some embodiments, the PDC can successfully release the payload resulting in about 60 to 100%release. In some embodiments, the PDC can successfully release the payload resulting in about 70 to 100%release. In some embodiments, the PDC can successfully release the payload resulting in about 70 to 90%release. In some embodiments, the PDC can successfully release the payload resulting in about 100%release. In some embodiments, the PDC can successfully release the payload resulting in about 90%release. In some embodiments, the PDC can successfully release the payload resulting in about 80%release. In some embodiments, the PDC can successfully release the payload resulting in about 70%release. In some embodiments, the PDC of the present application can successfully improve the solubility of the payload, resulting in an increase of solubility ranging from about 10%to 100 times higher. The increase in solubility may vary depending on the type of drug and protein, the method of conjugation, and experimental conditions. In some embodiments, the PDC of the present application can successfully improve the solubility of the payload by 30%to 80 times. In some embodiments, the PDC of the present application can successfully improve the solubility of the payload by 50%to 70 times. In some embodiments, the PDC of the present application can successfully improve the solubility of the payload by 70%to 60 times. In some embodiments, the PDC of the present application can successfully improve the solubility of the payload by 90%to 50 times. In some preferable embodiments, the PDC of the present application can successfully improve the solubility of the payload by 1 to 100 times. In some preferable embodiments, the PDC of the present application can successfully improve the solubility of the payload by 2 to 80 times. In some preferable embodiments, the PDC of the present application can successfully improve the solubility of the payload by 3 to 70 times. In some preferable embodiments, the PDC of the present application can successfully improve the solubility of the payload by 4 to 60 times. In some preferable embodiments, the PDC of the present application can successfully improve the solubility of the payload by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 time.
[1510] In some embodiments, the PDC of the present application has a half-life of less than 24 hours. In some embodiments, the PDC has a half-life of less than five hours. In some embodiments, the PDC has a half-life of less than three hours. In some embodiments, the PDC has a half-life of less than one hour. In some embodiments, the PDC has a half-life of between about 20 and 24 hours. In some embodiments, the PDC has a half-life of between about 20 and 22 hours. In some embodiments, the PDC has a half-life of about 20.42 hours. In some embodiments, the PDC has a half-life of between about two and five hours. In some embodiments, the PDC has a half-life of between about two and four hours. In some embodiments, the PDC has a half-life of about 2.54 hours. In some embodiments, the PDC has a half-life of between about zero and one hour. In some embodiments, the PDC has a half-life of between about 0 and 30 minutes. In some embodiments, the PDC has a half-life of between about 0 and 20 minutes. In some embodiments, the PDC has a half-life of between about 0 and 10 minutes. In some embodiments, the PDC has a half-life of between about zero and five minutes. In some embodiments, the PDC has a half-life of between about zero and one minute. In some embodiments, the PDC has a half-life of about 23.43 minutes. In some embodiments, the PDC has a half-life of about 22.75 minutes. In some embodiments, the PDC has a half-life of about 18.6 minutes. In some embodiments, the PDC has a half-life of about 17.83 minutes. In some embodiments, the PDC has a half-life of about 1.20 minutes. In some embodiments, the PDC has a half-life of about 0.99 minutes. In some embodiments, the PDC has a half-life of about 0.95 minutes.
[1511] In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into different skin layers, including stratum corneum, epidermis, and dermis. In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into stratum corneum and epidermis. In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into stratum corneum and dermis. In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into epidermis, and dermis. In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into stratum corneum, epidermis, and dermis. In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into stratum corneum. In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into epidermis. In some embodiments, the PDC of the present application can effectively deliver bioactive molecules and therapeutic compounds into dermis.
[1512] In some embodiments, the PDC of the present application can significantly reduce the circulatory exposure of the payloads, so as to prevent the payloads from being absorbed into systemic circulation and avoid their potential systemic adverse effects. In some preferable embodiments, the PDC of the present application can significantly avoid the circulatory exposure of the payloads. In some preferable embodiments, the payload in the PDC of the present application is undetectable in the systemic circulation.
[1513] In some embodiments of the PDC of the present application, one payload can be conjugated to one or more the same or different peptides via the linker. The PDC having one or more peptides of the present application can successfully improve the solubility of the payload, and can effectively deliver the payload into stratum corneum, epidermis, and dermis.
[1514] In some embodiments of the PDC of the present application, one or more the same or different payloads can be conjugated to one peptide via the linker. The PDC having one or more payloads of the present application can effectively deliver the payload into stratum corneum, epidermis, and dermis, and can effectively improve the efficacy of the payload.
[1515] Therapy
[1516] In one aspect, provided herein is a method of introducing a drug into a cell. In some embodiments, the method comprises contacting a cell with the peptide-drug conjugate described herein. In some embodiments, the method comprises contacting a biological membrane with a peptide-drug conjugate that contains a payload that is covalently attached to a peptide via a linker. In some embodiments, the compounds, compositions and methods described herein can be used to enhance transport of selected payloads across any of a number of biological membranes including, but not limited to, eukaryotic cell membranes. In some embodiments, the eukaryotic cell membranes of interest include membranes of epithelial cells, keratinocytes, epidermal cells and dermal cells.
[1517] For therapeutic applications, the compounds are administered to a mammal, in certain embodiments, a human, in a pharmaceutically acceptable dosage suitable for administration form such as those known in the art, and those discussed herein.
[1518] In some embodiments, the compounds and compositions described herein can be topically administered. In some embodiments, the topical compositions are in the form of a gel, ointment, cream, foam, spray, tonic, serum, paste, or lotion, more preferably in the form of spray, tonic or serum. In some embodiments, the spray formulation and the tonic formulation are formulated using the same unit formula. The difference of the spray formulations to the tonic formulations is that the spray formulations are administered by spraying to an affected site using a device.
[1519] In some embodiments, the compounds and compositions are used in the treatment of alopecia, particularly androgenetic alopecia, in the prevention or retardation of hair loss, and in the stimulation of hair growth and helps growth of new and healthy hairs in mammalians. In addition, it is predictable to those skilled in the art that the compounds and compositions may further be used in the treatment of alopecia areata, alopecia totalis, alopecia universalis, and other types of alopecia.
[1520] In certain embodiments, the compounds and compositions provided herein may be useful as cosmetics as described herein. In certain embodiments, the cosmetic is used for hair care.
[1521] Androgenetic Alopecia (AGA)
[1522] Androgenetic alopecia (AGA) is the most common form of hair loss, affecting both men and women. It is characterized by a progressive thinning of hair in specific patterns, often leading to significant hair loss. Increased dihydrotestosterone (DHT) level is the key factor responsible for AGA. Finasteride and Minoxidil are commonly used for the treatment for AGA. Finasteride inhibits 5α-reductase type II, an enzyme responsible for converting testosterone to DHT, reducing DHT levels and slowing hair loss. Minoxidil (applied topically) promotes hair growth by stimulating hair follicles and increasing blood flow to the scalp. Finasteride is commonly administered orally and exhibits systemic side effects. The finasteride PDCs of the present application enhance skin penetration and apply directly to the scalp; minimize systemic absorption and reduce the risk of side effects.
[1523] Examples
[1524] The examples are merely intended to illustrate embodiments and are not to be construed to limit the scope herein.
[1525] Example 1: General materials and methods
[1526] 1.1 Materials and Instruments
[1527] All reagents and solvents were purchased from commercial sources (Sigma-Aldrich, VWR, Fisher, TCI, Oakwood Chemicals, ChemScene) and used without purification unless otherwise noted. 1H NMR was recorded on Varian 400, 500, or 600 MHz spectrometers. LC-MS data were obtained on Agilent 1290 Infinity / Agilent 6100 Series Single Quad and Agilent 1260 Infinity / Agilent 6410 Triple Quadrupole. Peptides were synthesized using standard solid-phase peptide synthesis (SPPS) techniques. For peptides with a C-terminal carboxylic acid (-COOH) , 2-chlorotrityl chloride (2-CTC) resin was used. For peptides with a C-terminal carboxyl amide (-CONH2) , rink amide resin was employed. Fmoc (9-fluorenylmethyloxycarbonyl) chemistry was used for stepwise assembly of the peptide chains. After the synthesis of the sequence, the N-terminus was capped with either acetic acid or fatty acid. Following capping, the peptides were deprotected, cleaved from the resin, and purified. Peptide and PDC were purified using GX-281 Preparative HPLC System or Biotage Isolera One Flash Purification Chromatography System.
[1528] 1.2 Characterizations
[1529] NMR: 1H NMR was recorded on Varian 400, 500, or 600 MHz spectrometers. Chemical shifts are reported in delta (δ) units, expressed in parts per million (ppm) downfield from tetramethylsilane using protio-solvent (residual) as internal standard (CD3OD, δH = 3.31 ppm for 1H NMR, D2O, δH = 4.79 ppm for 1H NMR) . Data are reported as chemical shift (δ) , multiplicity (s= singlet, d = doublet, t = triplet, m = multiplet, br =broad) , and integration.
[1530] Abbreviations used in the Examples include:
[1531] Example 2: General synthetic procedure for synthesis of Finasteride-PDCs
[1532] General Scheme 1.
[1533] Step 1: Synthesis of Intermediate 1.
[1534] A stirring solution of Finasteride (3 g, 8.053 mmol, 1.0 eq, CAS: 98319-26-7) and DIPEA (3.33 mL, 20.132 mmol, 2.5 eq) in dry THF (30 mL) was chilled on ice for 5 min under argon. To the above mixture was added a solution of 4-Nitrophenyl chloroformate (3.246 g, 16.105 mmol, 2.0 eq) in dry THF (20 mL) dropwise at 0 ℃ under argon. The reaction was allowed to warm to room temperature and stirred for 24 h. The solvent was then evaporated, and the residue was purified by silica gel flash column chromatography (0 to 100%EtOAc / PE) to afford Intermediate 1 (1.82 g, 3.385 mmol, 42%yield) as white solid. ESI-MS m / z = 538.58 [M+H] + .
[1535] Step 2: Synthesis of Intermediate 2.
[1536] To an oven dried three-necked flask under nitrogen at room temperature equipped with a stir bar was added 1, 2-di (pyridin-2-yl) disulfane (9.429 g, 42.8 mmol) in 40 mL methanol purged with nitrogen. To this mixture was added 2-mercaptoethanol dropwise (1 mL, 14.27 mmol) . The solution turned yellow and was allowed to stir for two hours. The solvent was then removed in vacuo and flash chromatography was performed using 20%ethyl acetate and methylene chloride. The product was a yellow oil (2.288 g, 12.21 mmol, 85.6%yield) and homogeneous (one spot) by TLC Rf = 0.47 (5%EtOAc, DCM) . 1H NMR (400 MHz, Chloroform-d) δ8.50 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H) , 7.62 –7.53 (m, 1H) , 7.39 (dt, J = 8.1, 1.1 Hz, 1H) , 7.14 (ddd, J = 7.4, 5.0, 1.1 Hz, 1H) , 5.74 (s, 1H) , 3.79 (s, 2H) , 3.02 –2.85 (m, 2H) . ESI-MS m / z = 188 [M+H] +.
[1537] Step 3: Synthesis of Intermediate 3.
[1538] A stirring solution of Intermediate 2 (784 mg, 4.185 mmol, 1.5 eq) and NaH (60 %dispersion in mineral oil 100 mg, 4.185 mmol, 1.5 eq) in dry THF (15 mL) was chilled on ice under Ar. To the above mixture was added a solution of Intermediate 1 (1.5 g, 2.79 mmol, 1.0 eq) in dry DMF (15 mL) at 0 ℃ under argon, and the solution turned yellow immediately. The yellow solution was stirred at 0 ℃ for 2 h. The solvent was then evaporated. The residue was purified with silica gel column chromatography with 33%EtOAc / PE to afford Intermediate 3 (518 mg, 0.88 mmol, 31.7 %yield) as a white powder. ESI-MS m / z = 586.66 [M+H] +.
[1539] Step 4: Synthesis of PDC-01 to PDC-10.
[1540] PDC-01: A solution of Peptide-1 (58 mg, 0.041 mmol, 1.0 eq) , Intermediate 3 (48 mg, 0.082 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-01 (36.2 mg) as a white powder. Found mass: 472.92.
[1541] PDC-02: A solution of Peptide-2 (61 mg, 0.078 mmol, 1.0 eq) , Intermediate 3 (91 mg, 0.155 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-02 (67 mg) as a white powder. Found mass: 632.07.
[1542] PDC-03: A solution of Peptide-3 (68 mg, 0.042 mmol, 1.0 eq) , Intermediate 3 (49 mg, 0.084 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-03 (47 mg) as a white powder. Found mass: 697.94.
[1543] PDC-04: A solution of Peptide-4 (66.5 mg, 0.041 mmol, 1.0 eq) , Intermediate 3 (48 mg, 0.082 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-04 (34.8 mg) as a white powder. Found mass: 698.26.
[1544] PDC-05: A solution of Peptide-5 (67.7 mg, 0.047 mmol, 1.0 eq) , Intermediate 3 (55 mg, 0.082 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-05 (29.5 mg) as a white powder. Found mass: 643.50.
[1545] PDC-06: A solution of Peptide-6 (69.2 mg, 0.068 mmol, 1.0 eq) , Intermediate 3 (80 mg, 0.137 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-06 (24.4 mg) as a white powder. Found mass: 744.27.
[1546] PDC-07: A solution of Peptide-7 (65.6 mg, 0.031 mmol, 1.0 eq) , Intermediate 3 (37 mg, 0.663 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-07 (74.3 mg) as a white powder. Found mass: 514.00.
[1547] PDC-08: A solution of Peptide-8 (65.9 mg, 0.034 mmol, 1.0 eq) , Intermediate 3 (40 mg, 0.069 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-08 (15.5 mg) as a white powder. Found mass: 600.18.
[1548] PDC-09: A solution of Peptide-9 (69.2 mg, 0.049 mmol, 1.0 eq) , Intermediate 3 (57 mg, 0.097 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-09 (54.8 mg) as a white powder. Found mass: 634.23.
[1549] PDC-10: A solution of Peptide-10 (62.6 mg, 0.026 mmol, 1.0 eq) , Intermediate 3 (30.6 mg, 0.052 mmol, 2 eq) and dry DMF (2 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-10 (75 mg) as a white powder. Found mass: 719.08.
[1550] Example 3: General synthetic procedure of Minoxidil-PDCs
[1551] General Scheme 7-1.
[1552] Step 1: Synthesis of compound 3.
[1553] A round bottom flask was charged with 1 (500 mg, 2.39 mmol, 1.0 eq) , 2 (1044 mg, 2.62 mmol, 1.1 eq) , CsF (109 mg, 0.72 mmol, 0.3 eq. ) , and 5 mL of anhydrous DMF. The solution was allowed to stir for 2 hours at 60 ℃. The solvent was removed in vacuo. The resulting residue was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford compound 3 (320 m g, 32 %yield) .
[1554] Step 2: Synthesis of PDC-48 and PDC-49.
[1555] A solution of Peptide-1 (93 mg, 0.0426 mmol, 1.0 eq) , 3 (36 mg, 0.0852 mmol, 1.0 eq) and dry DMF (2.0 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-48 (89 mg, 81 %yield) as a white powder. Found mass: 862.2; 575.2; 431.6.
[1556] A solution of Peptide-2 (22.6 mg, 0.01 mmol, 1.0 eq) , 3 (8.7 mg, 0.021 mmol, 2.0 eq) and dry DMF (2.0 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-49 (15 mg, 57 %yield) as a white powder. Found mass: 861.2; 574.6; 431.2.
[1557] Step 3: Synthesis of PDC-50.
[1558] General Scheme 7-2.
[1559] A solution of Peptide-1 (60 mg, 0.027 mmol, 1.0 eq) , 4a (45 mg, 0.11 mmol, 4.0 eq) and dry DMF (2.0 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-50 (42 mg, 59 %yield) as a white powder. Found mass: 861.2; 574.6; 431.2.
[1560] Step 4: Synthesis of PDC-51.
[1561] General Scheme 7-3.
[1562] A solution of Peptide-1 (22.6 mg, 0.01 mmol, 1.0 eq) , 4b (8.7 mg, 0.021 mmol, 2.0 eq) and dry DMF (2.0 mL) was allowed to stir under argon for 24 h. The DMF solution was directly loaded onto a reverse phase column and purified by using (10 -100%) acetonitrile / water gradient (with 0.1%TFA added) . Appropriate fractions were lyophilized to afford PDC-51 (15 mg, 57 %yield) as a white powder. Found mass: 861.2; 574.6; 431.2.
[1563] Example 4: CCK-8 cell viability assay with HaCaT cells
[1564] HaCaT cells were counted. After cell counting, the cells were seeded at a density of 5000 cells per well in a 96-well cell culture plate. The plates were incubated overnight at 37℃ in a 5%CO2 incubator. Cells were treated with various concentrations of peptide at 0, 5, 2.5, 1.25, 0.625, and 0.3125 μM for 72h. After incubation, the culture medium was removed. An aliquot of 90 μL of serum-free DMEM was added to each well. An aliquot of 10 μL of CCK-8 detection reagent was added to each well and mixed thoroughly by vertexing. The mixture was incubated for 1 hour. The absorbance (OD value) at 450 / 650 nm was measured using a multifunctional microplate reader. Cell viability after treatment with transporter peptide is shown in Table 3.
[1565] Table 3. CCK-8 cell viability
[1566] Example 5: Cell uptake assay with HaCaT cells
[1567] HaCaT cells were seeded in a 96-well plate at 25, 000 cells per well and incubated at 37℃ with 5%CO2 for 24 hours. Cells were treated with various concentrations of the fluorescently labelled peptide at 0, 5, 2.5, 1.25, 0.625, and 0.3125 μM for 1h and 6h. After the treatment, Hoechst 33342 (10 μg / mL, 50 μL) was added for 10 minutes of nuclear staining. Images were captured under high-content objective lens for analysis. Images of Peptide-3 after 1 hour and 6 hours are shown in FIG. 7. Analogous experiments were performed for Peptides 4-27, 29 and 31 (images not shown) . Average cell fluorescence intensity per well and the percentage of positive cells were analyzed using CellScoring software under the 10x objective lens. Intracellular uptake after treatment with transporter peptide is shown in FIGS. 1-6 and Table 4.
[1568] Table 4. Intracellular uptake
[1569] NT indicates not tested.
[1570] Example 6: Release kinetics
[1571] The release rate and amount of payload from PDCs in the presence of dithiothreitol (DTT) were quantified using LC-MS. For the release study, PDC (50 μM) was mixed with DTT (5 mM) in PBS and incubated at 37℃. Aliquots were taken at set time intervals for LC-MS analysis, and the concentration of released payload was determined using the standard curve. Release kinetics were plotted over time and are shown in FIGS. 8-18 and Table 5. PDC-1 and PDC-2 could successfully release finasteride in the reducing environment, resulting in about 70%and 90%release (FIGS. 8-9) . Different linkers resulted in varying release kinetics, with PDC-48 exhibiting the fastest release, having a t1 / 2 of 1.2 min, while PDC-50 and PDC-51 showed much slower release rates with t1 / 2 values of 20.4 h and 2.54 h, respectively (FIGS. 10-13) . Both carbamate and carboxylic amide linkers could successfully facilitate the release of Minoxidil in a reducing environment. The carbamate linkage exhibited significantly faster release kinetics compared to the carboxylic acid linkage, with half-lives (t1 / 2) for PDC-48, PDC-49, PDC-50, and PDC-51, being 0.99 min, 1.20 min, 20.42 h, and 2.54 h, respectively (FIGS. 10-13) . The conjugation site influences release kinetics, as evidenced by the significantly shorter t1 / 2 of PDC-50 compared to PDC-51.
[1572] Table 5. Kinetics of peptide-drug conjugates
[1573] Example 7: Stability study of Finasteride PDCs
[1574] Stability studies for Finasteride PDCs were performed in PBS at 37 ℃. To evaluate conjugate stability, a 50 μM working solution was prepared by diluting 50 μL of a 1 mM stock solution with 950 μL PBS in a 1.5 mL centrifuge tube. The solution was incubated at 37℃ with shaking. At 0 minutes, 1 hour, 2 hours, and 6 hours, aliquots were collected for analysis. Conjugate peak areas were analyzed by LC-MS. The same procedure was applied to other conjugates, and the LC-MS peak areas were compared across the four time points. Finasteride PDC-02 and Finasteride PDC-09 are more stable conjugates among all 10 conjugates tested (FIG. 14) , Finasteride PDC-01 to Finasteride PDC-10:
[1575] Finasteride PDC-01
[1576] Finasteride PDC-02
[1577] Finasteride PDC-03
[1578] Finasteride PDC-04
[1579] Finasteride PDC-05
[1580] Finasteride PDC-06
[1581] Finasteride PDC-07
[1582] Finasteride PDC-08
[1583] Finasteride PDC-09
[1584] Finasteride PDC-10
[1585] Specifically, a 50 μM working solution was prepared by diluting 50 μL of a 1 mM stock solution with 950 μL PBS in a 1.5 mL centrifuge tube, adjust the pH to 5.0 and 7.4, respectively. The solution was incubated at 37℃ with shaking. At predetermined time points, aliquots were collected for analysis. Conjugate peak areas were analyzed by LC-MS. The same procedure was applied to other conjugates, and the LC-MS peak areas were compared across the four time points.
[1586] Finasteride PDC-02 and Finasteride PDC-09 are more stable conjugates at pH 5.0. Finasteride PDC-09 is more stable than Finasteride PDC-02 at pH 7.4 (FIG. 15) .
[1587] Example 8: Payload releasing study of Finasteride PDCs
[1588] Specifically, prepare a 1 mM stock solution of PLFNS by dissolving it in 100%methanol, then create a standard curve by diluting the stock to six concentrations, and analyze using LC-MS / MS. Similarly, prepare a 1 mM conjugate stock solution in methanol and a 10 mM GSH working solution in PBS (pH 7.4) . For the conjugate-GSH reaction, mix 50 μL of conjugate stock with 450 μL PBS and 500 μL GSH solution in a centrifuge tube. Incubate at 37℃ and 500 rpm, sampling at specific time points. Analyze the samples using LC-MS / MS, recording any dilution steps and methods.
[1589] In the presence of for 5 mM GSH, Finasteride PDC-02 and Finasteride PDC-09 gradually release finasteride, and the release ratios of Finasteride PDC-02 and Finasteride PDC-09 are 42%and 64%, respectively (FIG. 16) .
[1590] Example 9: Skin penetration study of Finasteride PDCs
[1591] Skin penetration study was conducted in 10-minute skin penetration study using Franzen diffusion cell and porcine skin. Specifically, add 500 μL of 100 μM finasteride and conjugate working solutions to the administration chamber, seal with parafilm, and cover with aluminum foil to protect from light. After a 10-minute skin incubation, collect receptor chamber samples and remaining test solution from the administration chamber, recording its volume. Rinse the administration chamber twice with 500 μL PBS, collecting and combining the rinses. For analysis, mix 500 μL of the administration chamber rinse and recovered solution with 500 μL of 10 mM GSH solution, incubate for 2 hours, and determine finasteride content using LC-MS. Similarly, mix 200 μL of the working solution with 200 μL of 10 mM GSH, incubate for 2 hours, and analyze using LC-MS. Receptor chamber samples are not analyzed at this stage. Calculate finasteride content in the administration chamber, the working solution, and standard curve results.
[1592] Finasteride PDC-02 and Finasteride PDC-09 achieved 25.67%and 26.99%penetration, respectively. Finasteride showed no detectable skin penetration. Therefore, conjugates showed higher skin penetration (FIG. 17 and FIG. 18) .
[1593] Example 10: Enzymatic inhibition towards 5α reductase of Finasteride PDCs
[1594] Specifically, ten male SD rats were fasted for 12 hours with access to water before euthanasia. The ventral prostate and epididymis were excised, weighed, minced on ice, and homogenized in pre-cooled buffer (1: 3, g / mL) . The homogenate was centrifuged at 1500g for 10 minutes at 4℃, and the supernatant was further centrifuged at 105, 000g for 1 hour at 4℃. The resulting pellet was resuspended in 1 mL of buffer and stored at -80℃. A 200 μL enzymatic reaction system was prepared to determine the concentration at which the positive control achieves a about 50%inhibition rate, which was used as a reference for comparing test substance inhibition rates. The positive control and the conjugates were tested at the same molar concentration. At the end of the enzymatic reaction, the reaction was terminated by adding 200 μL of pre-cooled acetonitrile containing 10 ng / mL rivaroxaban as an internal standard. After vortex mixing, the samples were centrifuged at 3220g for 10 minutes at 4℃. A 40 μL aliquot of the supernatant was mixed with 160 μL of pure water and analyzed by UPLC-MS / MS.
[1595] Finasteride PDC-09 achieved comparable inhibition efficacy as finasteride. Finasteride PDC-09 exhibited higher inhibition efficacy than Finasteride PDC-02 (FIG. 19) .
[1596] Example 11: Effects of Finasteride conjugates on testosterone induced cytotoxicity and DHT production in human dermal papilla cells (DPC cells)
[1597] Seed DPC cells at a density of 2 × 104 cells per well into a 96-well plate and allow them to attach for 48 hours before adding the treatment sample. After discarding the old medium, treat the cells with testosterone at different concentrations (10 μM or 40μM) and finasteride or finasteride PDC-09 at different concentrations (75 nM, 37.5nM, 18.75 nM or 9.375nM) as active pharmaceutical ingredient (API) , and incubate them at 37 ℃ with 5%CO2 for 48 hours. Check cell confluency under a microscope. Carefully aspirate the culture medium from each well, then add 90 μL of fresh serum-free medium to each well, followed by 10 μL of CCK-8 reagent. Measure the optical density at 450 nm using 650 nm as the reference wavelength.
[1598] After treated with testosterone, DPC cells’ viability recovery was comparable under finasteride treatment and finasteride PDC-09 (FIG. 20) .
[1599] Example 12: Plasma exposure of Finasteride conjugates in mini pigs
[1600] The formulations were applied topically to a 7 cm × 7 cm area on the back of mini pigs using a 1 mL syringe, with 0.5 mL of the test (finasteride PDC-09, referred to as group 1) or reference formulation (Caretopic, Fynzur, 2.275 mg / ml, referred to as group 2) . Each group includes two mini pigs. The application area was divided into nine equal sections, and approximately 0.056 mL of formulation was applied to each section. The site was shaved and cleaned at least three days prior to administration, using warm water or soap if necessary, and lightly cleaned before application. The reference formulation had a concentration of 2.275 mg / mL, and the test formulation was prepared at twice the molar concentration of the active ingredient relative to the reference formulation. Blood samples (0.5 mL) were collected into EDTA-2K tubes at 0 h, 0.25 h, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h and 24 h after transdermal administration, stored on crushed ice, and centrifuged at 1800g for 10 minutes at 4℃ within 1 hour. Plasma was then collected and stored at -80℃ within 0.5 hours. The drug concentration in the plasma was analyzed by LC-MS.
[1601] The plasma concentration and pharmacokinetic (PK) parameters at designated time points is shown in Table 5. Finasteride PDC-09 removes blood exposure of finasteride compared to Caretopic.
[1602] Table 5. Plasma concentration and PK parameters
[1603] BLQ: Below Limit of Quantitation
[1604] BQL: Below Quantitation Limit
[1605] NA: Not Available
[1606] #DIV / 0! : Results from any attempt to divide by zero
[1607] The lower limit of quantification is 0.01 ng / mL for finasteride, and is 0.025 ng / ml for finasteride PDC-09.
[1608] Example 13: Skin pharmacokinetics of Finasteride conjugates on mini pigs
[1609] The formulations were applied topically to a 7 cm × 7 cm area on the back of mini pigs using a 1 mL syringe, with 0.5 mL of the test (Finasteride PDC-09) or reference formulation (Caretopic, Fynzur, 2.275 mg / ml) . The application area was divided into nine equal sections, and approximately 0.056 mL of formulation was applied to each section. The site was shaved and cleaned at least three days prior to administration, using warm water or soap if necessary, and lightly cleaned before application. The reference formulation had a concentration of 2.275 mg / mL, and the test formulation (Finasteride PDC-09) was prepared at the same molar concentration of the active ingredient as the reference formulation. After the animals have reached the specified time points post-administration topically (0.5h, 1h, 6h, 24h) , they are euthanized for skin sample collection. At each time point, three mini pigs are euthanized in the test group and the reference group respectively. The entire skin from each application site (7cm x 7cm) is collected. Before collection, any residual formulation is cleaned using absorbent paper, followed by wiping the application site five times with a gauze pad soaked in saline and then three times with a gauze pad soaked in 75%alcohol. After cleaning the site, hair is shaved, and the skin is layered using a skin punch, first collecting the epidermis (0.1mm) . The top 0.1mm is discarded, and then the dermis layers of 0.3mm and 0.45mm thickness are collected. Three skin samples (epidermis, dermis 0.3mm, dermis 0.45mm) are taken from each application area to measure the drug concentration by LC-MS. More finasteride from Caretopic in the epidermis than that of finasteride PDC-09, meaning most finasteride PDC-09 will be delivered and released in dermis. Intact PDC was found in dermis, as well as finasteride, meaning the PDC releases finasteride in dermis (FIG. 21) .
[1610] Example 14: Real-time in vivo permeation testing
[1611] Conduct real-time in vivo permeation testing of the traceable substances in the samples by means of Raman spectroscopy. By tracking the characteristic peaks of the test samples applied to in vivo human skin, use Raman imaging diagrams to determine the permeation of traceable active substances in the test samples. Refer to T / SHRH 064-2024 <Transdermal penetration evaluation of cosmetic ingredients by Raman spectroscopy in vivo> for the detailed experimental procedure.
[1612] All subjects were informed of the study protocol and provided written informed consent prior to participation. Upon arrival, each subject was instructed to cleanse the designated test site using purified water. After cleansing, the subject remained seated in a temperature-and humidity-controlled environment for 30 minutes to allow for physiological equilibration of the skin.
[1613] The test sample (2.0 ± 0.2 mg) was uniformly applied to a defined 1 × 1 cm2 area on the volar forearm. Raman spectroscopic analysis was then performed on these areas to evaluate the dermal permeation profile of the sample.
[1614] Measurements were taken at predetermined time points, 0, 1, 2, 4, 6, 8, 10, 12 hours post-application. Within each test area, five measurement points were randomly selected, and each point was measured in triplicate to ensure data reliability and reproducibility.
[1615] The acquired Raman spectra were analyzed to assess the spatial distribution and relative skin permeability of the test sample over time.
[1616] Raman spectral imaging data processing includes spectral processing and data analysis. The spectral processing includes cosmic ray removal, spectral smoothing, background noise elimination, baseline calibration and spectral normalization. Univariate data analysis mainly focuses on biochemical substances corresponding to a specific peak position. Raman spectrum data analysis shows the distribution of the substances in human skin.
[1617] For data analysis, the Labspec software was used to perform baseline calibration of Raman spectra and confirmation of characteristic peak positions. The processed Raman spectra data were calculated, including peak intensity, peak displacement, peak area and half-peak width, etc. At the same time, Labspec software was used to analyze the corresponding peak intensity at different depths and plot its spatial distribution.
[1618] The penetration behavior of the product was determined by utilizing its characteristic Raman signals that are distinct from the intrinsic signals of the skin to confirm its distribution in different skin depth space.
[1619] Sample preparation:
[1620] Sample 1: Weighed 8.0 mg of finasteride into a vial, added 270 μL of 1, 2-hexanediol, and sonicated to dissolve. Then, 2930 μL of PBS (pH 5.0) was added, followed by sonication at 100 Hz for 10 min to obtain a white, semi-transparent solution. The resulting mixture was diluted with PBS (pH 5.0) to achieve a final finasteride concentration of 0.114% (w / v) .
[1621] Sample 2: Finasteride PDC-09 was weighed and diluted with a 20 mM sodium acetate solution (pH 4.6) to a total mass of 2 g. A Finasteride PDC-09 solution was thereby obtained at the same molar concentration as Sample 1.
[1622] Table 6. Penetrating ability of Samples 1-2
[1623] As shown in Table 6, Figure 22, and Figure 23, the results indicate that Finasteride conjugated with peptide (Finasteride PDC-09) exhibits superior skin penetration compared to free Finasteride, demonstrating higher relative permeability and deeper maximum penetration depths.
[1624] Example 15: Human skin-occlusive patch test
[1625] Test Method: Safety and Technical Standards for Cosmetics (Version 2015) , Chapter VII: Human skin patch test
[1626] Sample: Finasteride PDC-09 was weighed and diluted with a 20 mM sodium acetate solution (pH 4.6) to obtain a test solution at the same molar concentration as the reference formulation (Caretopic, Fynzur, 2.275 mg / mL) .
[1627] Negative control: Blank
[1628] Procedure:
[1629] A qualified patch test chamber with a surface area not exceeding 50 mm2 and a depth of approximately 1 mm was selected. The test substance was applied to the chamber at a dose of approximately 0.020–0.025 g (for solids or semi-solids) or 0.020–0.025 mL (for liquids) . The patch chambers containing the test substance and the negative control were affixed to the volar side of the subject’s forearm. After 24 hours, the chambers were removed. Skin reactions were evaluated at 30 minutes (after pressure marks had faded) , 24 hours, and 48 hours following patch removal, based on the criteria in Table 1. All observations were documented accordingly.
[1630] A total of 33 subjects were enrolled in this study, and all 33 completed the trial. Using a systematic sampling method, the first 30 subjects were selected for statistical analysis (subjects No. 31, 32, and 33 were excluded accordingly) . The final valid dataset included 30 subjects-7 males and 23 females-aged between 32 and 60 years.
[1631] Table 7. Subjects age analysis
[1632] Table 8. Skin reaction grading criteria for skin occlusive patch test
[1633] Table 9. Results of skin occlusive patch test
[1634] Results: The results showed that all 30 subjects exhibited a skin reaction score of 0 at 0.5, 24, and 48 hours after removal of the patch test chamber, with no adverse skin reactions observed.
[1635] *****
[1636] The examples set forth above are provided to give those of ordinary skill in the art with a complete disclosure and description of how to make and use the claimed embodiments, and are not intended to limit the scope of what is disclosed herein. Modifications that are obvious to persons of skill in the art are intended to be within the scope of the following claims. All publications, patents, and patent applications cited in this specification are incorporated herein by reference as if each such publication, patent or patent application were specifically and individually indicated to be incorporated herein by reference.
Claims
1.A conjugate or a pharmaceutically acceptable salt or cosmetically acceptable salt thereof, wherein the conjugate comprises a peptide and a payload, with the peptide covalently binds to the payload via a linker, wherein the peptide has the following structure of Formula I:R1-W1-X-PP-W2-R2 (Formula I)wherein:R1 is an N-terminal modification;R2 is absent or a C-terminal modification;each of W1 and W2 is independently selected from a direct bond or a linking moiety;X is absent or a targeting moiety;wherein one or more of W1, W2 and X are connected to the linker;PP is selected from:(1) oligo-arginine or oligo-arginine-analog, or(2) oligo-arginine or oligo-arginine-analog, which is implanted with at least one spacer;wherein the oligo-arginine is an oligomer of arginine, wherein the arginine can be L or D form; and the oligo-arginine-analog is an oligomer of an arginine analog containing guanidyl;wherein one payload can bind to one or more the same or different peptides via the linker, or one or more the same or different payloads can bind to one peptide via the linker;wherein the payload is an agent for the treatment of androgenetic alopecia.2.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 1, wherein the linker is a cleavable linker or a non-cleavable linker, preferably a cleavable linker, more preferably a linker that can be induced for cleavage and traceless release by reduction, and is preferably selected from the group comprising wherein t is an integer of from 1 to 5, preferably 1 to 3;and more preferably, the linker iswherein t is 1, and U is O.3.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 1 or 2, wherein the payload is selected from the group comprising finasteride, minoxidil, dutasteride and spironolactone, and is preferably finasteride.4.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-3, wherein one payload can bind to 1-2 the same or different peptides via the linker, or 1-2 the same or different payloads can bind to one peptide via the linker; and preferably, one payload binds to one peptide by the linker.5.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-4, wherein R1 is an N-terminal modification selected from the group comprising acetylation, lipidation, PEGylation, cholesterol modification, polycyclic aromatic hydrocarbon modification, glycosylation, fluorination, sulfonation; preferably, acetyl modification, fatty acid modification, and pyrenebutyrate modification.6.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-5, wherein R2 is a C-terminal modification selected from the group comprising amidation, alkylation, lipidation, PEGylation, cholesterol modification, and polycyclic aromatic hydrocarbon modification; preferably, NH2.7.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-6, wherein the linking moiety is preferably cysteine or lysine, wherein the cysteine or lysine can be L or D form.8.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-7, wherein the targeting moiety is selected from the group comprising transferrin, a Penetration Accelerating Sequence (PAS) , a Nuclear Localization Signal (NLS) sequence, an Endosomal Escape Enhancer, and a Heparin Sulfate Binding Peptides;and preferably, the targeting moiety is a NLS sequence, the NLS sequence can be selected from the group comprising PKKKRKV (NLS1) , PKLKRQ (NLS2) , PAAKRVKLD (NLS3) , RPRK, RRARRPRG, GKRKLITSEEERSPAKRGRKS, KGKKGRTQKEKKAARARSKGKN, RKRCAAGVGGGPAGCPAPGSTPLKKPRR, RKPVTAQERQREREEKRRRRQERAKEREKRRQERER, RSGGNHRRNGRGGRGGYNRRNNGYHPY, TLLLRETMNNLGVSDHAVLSRKTPQPY, PGKMDKGEHRQERRDRPY, GKKKKGKPGKRREQRKKKRRT, SANKVTKNKSNSSPYLNKRKGKPGPDS, andVHSHKKKKIPTSPTFTTPKTLTLRRQPKYPRKSAPRRNKLDHY;and optionally, the targeting moiety is connected to the linker, preferably by Cys or Lys residue in the targeting moiety.9.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-8, wherein the oligo-arginine or oligo-arginine-analog is implanted with the spacer in such a way that one spacer is implanted in between every two adjacent residues in the oligo-arginine or oligo-arginine-analog, or in such a way that the spacer and the residues in the oligo-arginine or oligo-arginine-analog collectively form 2 or more unit structures of (X1X2X3) , wherein 0-1 in X1, X2 and X3 is the spacer and the other 2 or 3 are the residues of the oligo-arginine or oligo-arginine-analog, and preferably, the spacer and the oligo-arginine or oligo-arginine-analog collectively form 2-12, preferably 2-5 unit structures of (X1X2X3) ,and more preferably, all the unit structures of (X1X2X3) are the same.10.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 9 wherein the spacer consists of 1-3, preferably 1 residue.11.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 9 or 10, wherein the residue in the spacer is selected from the group comprising β-alanine (βAla) , γ-Aminobutyric acid, Aminohexanoic acid (Ahx) , proline, and tryptophan, preferably β-alanine (βAla) ; wherein the residue can be L or D form.12.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims1-11, wherein the residue in the oligo-arginine-analog is preferably selected from the group comprising2- (6-guanidylhexyl) amino acetic acid (GuanidylC6NHPeptoid) ,2- (4-guanidylbutyl) amino acetic acid (GuanidylC4NHPeptoid) , and2- (7-guanidylheptyl) amino acetic acid (GuanidylC7NHPeptoid) .13.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-12, wherein the PP is oligo-arginine or oligo-arginine-analog.14.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 13, wherein the peptide has the following structure of Formula II:R1-W1-PP-R2 (Formula II)wherein R1, W1, PP and R2 are the same as defined in claim 1, and wherein R1 is a fatty acid modification or acetyl modification and is preferably acetyl modification, R2 is NH2, W1 is Cys or Lys, and is preferably Cys, and the PP is oligo-arginine; and wherein W1 is connected to the linker.15.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 13 or 14, wherein the peptide is selected from the group comprising:Ac-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 47) ,C8-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 48) ,C10-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 49) ,C12-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 50) ,C14-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 51) ,C16-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 52) ,C18-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 53) ,C20-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 54) ,C22-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 55) ,Ac-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 56) ,C8-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 57) ,C10-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 58) ,C12-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 59) ,C14-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 60) ,C16-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 61) ,C18-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 62) ,C20-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 63) ,C22-Lys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 64) ,Ac-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 65) ,C8-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 66) ,C10-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 67) ,C12-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 68) ,C14-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 69) ,C16-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 70) ,C18-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 71) ,C20-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 72) ,C22-Cys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 73) ,Ac-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 74) ,C8-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 75) ,C10-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 76) ,C12-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 77) ,C14-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 78) ,C16-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 79) ,C18-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 80) ,C20-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 81) ,C22-Lys-DArg-DArg-DArg-DArg-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 82) ;and preferably the peptide is Ac-Cys-DArg-DArg-DArg-DArg-CONH2 (SEQ. ID No. 47) .16.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-12, wherein the PP is oligo-arginine or oligo-arginine-analog implanted with the spacer in such a way that one spacer is implanted in between every two adjacent residues in the oligo-arginine or oligo-arginine-analog, wherein the spacer consists of one residue, and preferably the residue is β-alanine.17.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 16, wherein the peptide has the following structure of Formula II:R1-W1-PP-R2 (Formula II)wherein R1, W1, PP and R2 are the same as defined in claim 1, and wherein R1 is a fatty acid modification or acetyl modification, and is preferably fatty acid modification, R2 is NH2, W1 is Cys or Lys, and is preferably Cys, and the PP is the same as defined in claim 16; and wherein W1 is connected to the linker.18.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 16-17, wherein the peptide is selected from the group comprising:Ac-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 101) ,C8-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 102) ,C10-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 103) ,C12-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 104) ,C14-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 105) ,C16-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 106) ,C18-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 107) ,C20-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 108) ,C22-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 109) ,Ac-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 110) ,C8-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 111) ,C10-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 112) ,C12-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 113) ,C14-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 114) ,C16-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 115) ,C18-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 116) ,C20-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 117) ,C22-Lys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 118) ,and preferably the peptide is C16-Cys-Arg- (βAla-Arg) 4-CONH2 (SEQ. ID No. 106) .19.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-12, wherein the PP is oligo-arginine or oligo-arginine-analog implanted with the spacer in such a way that the spacer and the oligo-arginine or oligo-arginine-analog collectively form the same unit structures of (X1X2X3) , wherein X2 is the spacer and X1 and X3 are arginine or arginine-analog, wherein the spacer consists of one residue,and preferably, the residue is Aminohexanoic acid or β-alanine.20.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 19, wherein the peptide has the following structure of Formula IV:R1-PP-W2-R2 (Formula IV)wherein R1, PP, W2 and R2 are the same as defined in claim 1, and wherein R1 is a fatty acid modification or acetyl modification, R2 is NH2, W12 is Cys or Lys, and is preferably Cys, and the PP is the same as defined in claim 19; and wherein W2 is connected to the linker.21.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 19, wherein the peptide is selected from the group comprising:Ac- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 238) ,C8- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 239) ,C10- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 240) ,C12- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 241) ,C14- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 242) ,C16- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 243) ,C18- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 244) ,C20- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 245) ,C22- (Arg-Ahx-Arg) 4-Cys-CONH2 (SEQ. ID No. 246) ,Ac- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 247) ,C8- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 248) ,C10- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 249) ,C12- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 250) ,C14- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 251) ,C16- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 252) ,C18- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 253) ,C20- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 254) ,C22- (Arg-Ahx-Arg) 4-Lys-CONH2 (SEQ. ID No. 255) ,Ac- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 256) ,C8- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 257) ,C10- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 258) ,C12- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 259) ,C14- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 260) ,C16- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 261) ,C18- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 262) ,C20- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 263) ,C22- (Arg-βAla-Arg) 4-Cys-CONH2 (SEQ. ID No. 264) ,Ac- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 265) ,C8- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 266) ,C10- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 267) ,C12- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 268) ,C14- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 269) ,C16- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 270) ,C18- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 271) ,C20- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 272) ,C22- (Arg-βAla-Arg) 4-Lys-CONH2 (SEQ. ID No. 273) .22.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-12, wherein the PP is oligo-arginine or oligo-arginine-analog implanted with the spacer in such a way that the spacer and the oligo-arginine or oligo-arginine-analog collectively form the same unit structures of (X1X2X3) , wherein X1 is proline and X2 and X3 are arginine or arginine-analog, wherein proline and arginine can be L or D form.23.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 22, wherein the peptide has the following structure of Formula II:R1-W1-PP-R2 (Formula II)wherein R1, W1, PP and R2 are the same as defined in claim 1, and wherein R1 is a fatty acid modification or acetyl modification, and is preferably fatty acid modification, R2 is absent or NH2, W1 is Cys or Lys, and is preferably Cys, and the PP is the same as defined in claim 22; and wherein W1 is connected to the linker.24.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 22, wherein the peptide has the following structure of Formula VI:R1-W1-X-PP-R2 (Formula VI) wherein R1, W1, X, PP and R2 are the same as defined in claim 1, and wherein R1 is a fatty acid modification or acetyl modification, and is preferably fatty acid modification, R2 is absent or NH2, W1 is Cys or Lys, and is preferably Cys, X is a NLS sequence, and is preferably NLS1, and the PP is the same as defined in claim 22; and wherein W1 and / or X are connected to the linker, wherein if X is connected to the linker, it is preferably connected by Cys or Lys residue in X.25.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to claim 22, wherein the peptide is selected from the group comprising:Ac-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 346) ,C8-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 347) ,C10-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 348) ,C12-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 349) ,C14-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 350) ,C16-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 351) ,C18-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 352) ,C20-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 353) ,C22-Cys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 354) ,Ac-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 355) ,C8-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 356) ,C10-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 357) ,C12-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 358) ,C14-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 359) ,C16-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 360) ,C18-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 361) ,C20-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 362) ,C22-Lys- (DPro-Arg-D-Arg) 3-COOH (SEQ. ID No. 363) ,Ac-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 364) ,C8-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 365) ,C10-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 366) ,C12-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 367) ,C14-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 368) ,C16-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 369) ,C18-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 370) ,C20-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 371) ,C22-Cys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 372) ,Ac-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 373) ,C8-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 374) ,C10-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 375) ,C12-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 376) ,C14-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 377) ,C16-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 378) ,C18-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 379) ,C20-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 380) ,C22-Lys- (DPro-Arg-Arg) 5-COOH (SEQ. ID No. 381) ,Ac-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 382) ,C8-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 383) ,C10-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 384) ,C12-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 385) ,C14-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 386) ,C16-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 387) ,C18-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 388) ,C20-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 389) ,C22-Cys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 390) ,Ac-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 391) ,C8-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 392) ,C10-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 393) ,C12-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 394) ,C14-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 395) ,C16-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 396) ,C18-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 397) ,C20-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 398) ,C22-Lys- (DPro-Arg-Arg) 4-COOH (SEQ. ID No. 399) ,Ac-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 400) ,C8-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 401) ,C10-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 402) ,C12-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 403) ,C14-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 404) ,C16-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 405) ,C18-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 406) ,C20-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 407) ,C22-Cys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 408) ,Ac-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 409) ,C8-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 410) ,C10-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 411) ,C12-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 412) ,C14-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 413) ,C16-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 414) ,C18-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 415) ,C20-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 416) ,C22-Lys- (DPro-Arg-Arg) 3-CONH2 (SEQ. ID No. 417) ,Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 418) (NLS1-pRR3) ,C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 419) (NLS1-pRR3) ,C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 420) (NLS1-pRR3) ,C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 421) (NLS1-pRR3) ,C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 422) (NLS1-pRR3) ,C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 423) (NLS1-pRR3) ,C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 424 (NLS1-pRR3) ,C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 425) (NLS1-pRR3) ,Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 426) (NLS1-pRR3) ,C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 427) (NLS1-pRR3) ,C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 428) (NLS1-pRR3) ,C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 429) (NLS1-pRR3) ,C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 430) (NLS1-pRR3) ,C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 431) (NLS1-pRR3) ,C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 432) (NLS1-pRR3) ,C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 433) (NLS1-pRR3) ,Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 434) (NLS2-pRR3) ,C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 435) (NLS2-pRR3) ,C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 436) (NLS2-pRR3) ,C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 437) (NLS2-pRR3) ,C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 438) (NLS2-pRR3) ,C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 439) (NLS2-pRR3) ,C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 440) (NLS2-pRR3) ,C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 441) (NLS2-pRR3) ,C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 442) (NLS2-pRR3) ,Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 443) (NLS2-pRR3) ,C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 444) (NLS2-pRR3) ,C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 445) (NLS2-pRR3) ,C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 446) (NLS2-pRR3) ,C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 447) (NLS2-pRR3) ,C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 448) (NLS2-pRR3) ,C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 449) (NLS2-pRR3) ,C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 450) (NLS2-pRR3) ,C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 451) (NLS2-pRR3) ,Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 452) (NLS3-pRR3) ,C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 453) (NLS3-pRR3) ,C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 454) (NLS3-pRR3) ,C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 455) (NLS3-pRR3) ,C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 456) (NLS3-pRR3) ,C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 457) (NLS3-pRR3) ,C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 458) (NLS3-pRR3) ,C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 459) (NLS3-pRR3) ,C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 460) (NLS3-pRR3) ,Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 461) (NLS3-pRR3) ,C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 462) (NLS3-pRR3) ,C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 463) (NLS3-pRR3) ,C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 464) (NLS3-pRR3) ,C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 465) (NLS3-pRR3) ,C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 466) (NLS3-pRR3) ,C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 467) (NLS3-pRR3) ,C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 468) (NLS3-pRR3) ,C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 3-CONH2, (SEQ. ID No. 469) (NLS3-pRR3) ,Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 470) (NLS1-pRR4) ,C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 471) (NLS1-pRR4) ,C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 472) (NLS1-pRR4) ,C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 473) (NLS1-pRR4) ,C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 474) (NLS1-pRR4) ,C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 475) (NLS1-pRR4) ,C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 476) (NLS1-pRR4) ,C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 477) (NLS1-pRR4) ,Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 478) (NLS1-pRR4) ,C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 479) (NLS1-pRR4) ,C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 480) (NLS1-pRR4) ,C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 481) (NLS1-pRR4) ,C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 482) (NLS1-pRR4) ,C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 483) (NLS1-pRR4) ,C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 484) (NLS1-pRR4) ,C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 485) (NLS1-pRR4) ,Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 486) (NLS2-pRR4) ,C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 487) (NLS2-pRR4) ,C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 488) (NLS2-pRR4) ,C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 489) (NLS2-pRR4) ,C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 490) (NLS2-pRR4) ,C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 491) (NLS2-pRR4) ,C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 492) (NLS2-pRR4) ,C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 493) (NLS2-pRR4) ,C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 494) (NLS2-pRR4) ,Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 495) (NLS2-pRR4) ,C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 496) (NLS2-pRR4) ,C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 497) (NLS2-pRR4) ,C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 498) (NLS2-pRR4) ,C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 499) (NLS2-pRR4) ,C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 500) (NLS2-pRR4) ,C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 501) (NLS2-pRR4) ,C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 502) (NLS2-pRR4) ,C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 503) (NLS2-pRR4) ,Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 504) (NLS3-pRR4) ,C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 505) (NLS3-pRR4) ,C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 506) (NLS3-pRR4) ,C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 507) (NLS3-pRR4) ,C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 508) (NLS3-pRR4) ,C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 509) (NLS3-pRR4) ,C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 510) (NLS3-pRR4) ,C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 511) (NLS3-pRR4) ,C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 512) (NLS3-pRR4) ,Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 513) (NLS3-pRR4) ,C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 514) (NLS3-pRR4) ,C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 515) (NLS3-pRR4) ,C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 516) (NLS3-pRR4) ,C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 517) (NLS3-pRR4) ,C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 518) (NLS3-pRR4) ,C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 519) (NLS3-pRR4) ,C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 520) (NLS3-pRR4) ,C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 4-CONH2, (SEQ. ID No. 521) (NLS3-pRR4) ,Ac-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 522) (NLS1-pRR5) ,C8-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 523) (NLS1-pRR5) ,C10-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 524) (NLS1-pRR5) ,C12-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 525) (NLS1-pRR5) ,C14-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 526) (NLS1-pRR5) ,C18-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 527) (NLS1-pRR5) ,C20-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 528) (NLS1-pRR5) ,C22-Cys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 529) (NLS1-pRR5) ,Ac-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 530) (NLS1-pRR5) ,C8-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 531) (NLS1-pRR5) ,C10-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 532) (NLS1-pRR5) ,C12-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 533) (NLS1-pRR5) ,C14-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 534) (NLS1-pRR5) ,C18-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 535) (NLS1-pRR5) ,C20-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 536) (NLS1-pRR5) ,C22-Lys-Pro-Lys-Lys-Lys-Arg-Lys-Val- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 537) (NLS1-pRR5) ,Ac-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 538) (NLS2-pRR5) ,C8-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 539) ,C10-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 540) ,C12-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 541) ,C14-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 542) ,C16-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 543) ,C18-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 544) ,C20-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 545) ,C22-Cys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2 (NLS2-pRR5) , (SEQ. ID No. 546) ,Ac-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 547) (NLS2-pRR5) ,C8-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 548) (NLS2-pRR5) ,C10-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 549) (NLS2-pRR5) ,C12-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 550) (NLS2-pRR5) ,C14-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 551) (NLS2-pRR5) ,C16-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 552) (NLS2-pRR5) ,C18-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 553) (NLS2-pRR5) ,C20-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 554) (NLS2-pRR5) ,C22-Lys-Pro-Lys-Leu-Lys-Arg-Gln- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 555) (NLS2-pRR5) ,Ac-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 556) (NLS3-pRR5) ,C8-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 557) (NLS3-pRR5) ,C10-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 558) (NLS3-pRR5) ,C12-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 559) (NLS3-pRR5) ,C14-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 560) (NLS3-pRR5) ,C16-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 561) (NLS3-pRR5) ,C18-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 562) (NLS3-pRR5) ,C20-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 563) (NLS3-pRR5) ,C22-Cys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 564) (NLS3-pRR5) ,Ac-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 565) (NLS3-pRR5) ,C8-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 566) (NLS3-pRR5) ,C10-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 567) (NLS3-pRR5) ,C12-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 568) (NLS3-pRR5) ,C14-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 569) (NLS3-pRR5) ,C16-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 570) (NLS3-pRR5) ,C18-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 571) (NLS3-pRR5) ,C20-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 572) (NLS3-pRR5) ,C22-Lys-Pro-Ala-Ala-Lys-Arg-Val-Lys-Leu-Asp- (DPro-Arg-Arg) 5-CONH2, (SEQ. ID No. 573) (NLS3-pRR5) .26.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-25, wherein the payload is Finasteride, and the conjugate is preferably selected from: 27.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-26, wherein the conjugate is 28.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-26, wherein the conjugate is: 29.The conjugate or pharmaceutically acceptable salt or cosmetically acceptable salt thereof according to any one of claims 1-25, wherein the payload is Minoxidil, and the conjugate is preferably selected from: 30.A pharmaceutical composition comprising the conjugate or pharmaceutically acceptable salt thereof according to any one of claims 1-29, and a pharmaceutical excipient, preferably the pharmaceutical composition is selected from the group comprising ointment, cream, solution, tincture, gel, spray, powder, foam, spirit, powder, lotion, oil, emulsion, suspension, paste, film, and aerosol.31.A cosmetic composition comprising the conjugate or cosmetically acceptable salt thereof according to any one of claims 1-29, preferably the cosmetic composition is selected from the group comprising skin lotion, milk lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, powder, hair tonic, hear cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, solgel, emulsion, oil, wax and aerosol.32.The conjugate or pharmaceutically acceptable salt thereof according to any one of claims 1-29 or the pharmaceutical composition according to claim 30 for use in the treatment of androgenetic alopecia.33.The conjugate or cosmetically acceptable salt thereof according to any one of claims 1-29 or the cosmetic composition according to claim 31 for use in cosmetic application.34.Use of the conjugate or pharmaceutically acceptable salt thereof according to any one of claims 1-29 or the pharmaceutical composition according to claim 30 for the manufacture of a medicament for the treatment of androgenetic alopecia.35.Use of the conjugate or cosmetically acceptable salt thereof according to any one of claims 1-29 or the cosmetic composition according to claim 31 for the manufacture of a cosmetic.36.A method for treating androgenetic alopecia, comprising administering the conjugate or pharmaceutically acceptable salt thereof according to any one of claims 1-29 or the pharmaceutical composition according to claim 30 to a subject in need thereof.37.The method according to claim 36, wherein the conjugate or pharmaceutically acceptable salt thereof or the pharmaceutical composition is topically administered to the skin.38.A cosmetic method, comprising topically applying the conjugate or cosmetically acceptable salt thereof according to any one of claims 1-29 or the cosmetic composition according to claim 31 to a subject in need thereof.