22 results about "Stapled peptide" patented technology

The application discloses a stapled peptide compound for selectively degrading MYC protein, a preparation method and application thereof; the compound is sequentially connected in the N-terminal to C-terminal direction by a peptide recognition segment, a flexible linker and a chaperone-mediated autophagy recognition motif KFERQ or a similar motif; the peptide recognition segment is introduced by an (i, i+7) site alkenyl amino acid and a Grubbs catalytic RCM reaction to form a full carbon hydrogen stapling bridge to stabilize the alpha-helix conformation; stapled modification of a typical compound MAX-7 significantly improves the alpha-helix content, the protease stability and the cell penetration, so that the compound can efficiently enter cells and be located in lysosomes, and MYC protein is selectively degraded through the CMA pathway; in-vitro experiments show that MAX-7 can inhibit the proliferation, migration and invasion of various MYC-driven tumor cells, and induce apoptosis; the application provides a brand-new lysosome-directed degradation strategy for the "undruggable" target MYC, and establishes a universal technical platform which can be popularized to other difficult drug proteins.

Methods and compositions are provided for extending the half-life of a therapeutic agent A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.

The invention belongs to the field of polypeptide medicines, and particularly relates to stapled peptide and application thereof. According to the present invention, Ac-LKRVWKRVFKLLKS5YWRS5LKKPVR-NH2 is adopted as a peptide chain template, and an amino acid residue 15Y is replaced by K so as to obtain the target stapled peptide SLP-8; compared with the template polypeptide, the hemolytic activity of the obtained stapled peptide SLP-8 is obviously improved.

The application discloses a kind of double S-alkyl isothiourea derivatives, its preparation method and application, belong to biochemical technical field.The double S-alkyl isothiourea derivative is the compound shown in general formula 1 or its pharmaceutically acceptable salt, in formula, R is saturated alkane or unsaturated alkane;X is any one of i, ii and iii;I is branched C1-C 20 Saturated alkane or straight-chain C1-C 20 Saturated alkane;II is unsaturated alkane;III is heteroatom-substituted alkane.The application further discloses a preparation method and application of the above-mentioned double S-alkyl isothiourea derivative, a stapled peptide and a preparation method thereof.The double S-alkyl isothiourea derivative of the application can be used for stapled peptide synthesis, and the obtained stapled peptide containing guanidyl structure has the advantages of good water solubility and strong membrane permeability in addition to various advantages of traditional all-carbon hydrogen stapled peptide in polypeptide structure modification.

Provided herein are stapled peptide-antibody conjugates (SPACs) comprising a stapled peptide conjugated to an antibody or antigen-binding fragment thereof. In certain embodiments, the stapled peptide is conjugated to the antibody or antigen-binding fragment thereof via a linker. In certain embodiments, the SPACs provided herein can be used to deliver stapled peptides to cells (e.g., cancer cells) with relatively high selectivity and relatively low off-target toxicity. Also provided herein are pharmaceutical compositions and kits comprising the SPACs described herein, methods of using the same (e.g., to treat cancer and / or inhibit tumor growth in a subject), and methods of preparing the same.

The application discloses a stapling peptide targeting TRIB3 / SSRP1 interaction and application of the stapling peptide in preparation of anti-multiple myeloma drugs. Through a series of experiments such as immunoprecipitation coupling mass spectrometry, it is found that TRIB3 directly interacts with SSRP1 protein in multiple myeloma cells, thereby playing a role in promoting malignant proliferation of multiple myeloma, and TRIB3 promotes degradation of the SSRP1 protein through a ubiquitin-proteasome pathway. The stapling peptide 7695-SP5 inhibits malignant proliferation of multiple myeloma by specifically inhibiting TRIB3 / SSRP1 protein interaction. The stapling peptide 7695-SP5 can be used as a TRIB3 / SSRP1 protein interaction inhibitor to treat diseases caused by increased expression of TRIB3 and SSRP1 proteins, such as multiple myeloma, and is expected to be developed into a novel anti-tumor drug.

The invention belongs to the field of polypeptide drugs, and particularly relates to an antibacterial polypeptide and application thereof. According to the invention, Rink amide MBHA amino resin is used as a solid phase carrier, modification and transformation are carried out according to an amino acid sequence of a template polypeptide raniseptinPL: Ac-GVFDTVKKIGKAVGKFALGVAKNYLNS-NH2, and on the basis of retaining key amino acid residues, original amino acids are respectively replaced by S5 and R8 at amino acid positions i, i + 4 and i and i + 7, so that a target stapling peptide is obtained. Compared with a template polypeptide PL-0, the obtained stapled peptide has the advantage that the antibacterial activity on staphylococcus aureus, enterococcus faecium, enterococcus faecalis and staphylococcus epidermidis can be obviously improved.

The application belongs to the field of polypeptide drugs, and particularly relates to an antibacterial polypeptide and application thereof in pharmacy. The application takes Rink amide MBHA amino resin as a solid phase carrier, and modifies and transforms according to a template polypeptide raniseptin PL:Ac-GVFDTVKKIGKAVGKFALGVAKNYLNS-NH2 amino acid sequence, wherein amino acid residues 19G and 26N are replaced by R8 and S5, to obtain a target stapled peptide PL-16. The stapled peptide PL-16 can significantly improve the antibacterial activity on Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis and Staphylococcus epidermidis relative to the template polypeptide PL-0.

The invention belongs to the technical field of polypeptide drugs, and particularly relates to a series of polypeptides with an anti-cancer effect and application thereof. According to the invention, Rink amide MBHA amino resin is used as a solid phase carrier, modification is carried out according to an amino acid sequence of a template polypeptide Hymenochirin-1Pa (H-0): Ac-LKLSPKTKDTLKKVLKGAIKGAIAIASAMA-NH2, and on the basis of retaining key amino acid residues, original amino acids are replaced by R8 and S5 at the positions of i and i + 7 amino acids, so that the target stapling peptide is obtained. Compared with a template polypeptide H-0, the obtained stapled peptide has the advantage that the anti-tumor activity on human liver cancer cells Huh7, human non-small cell lung cancer cells A549, glioma cells U87 and colon cancer cells T84 can be obviously improved.

This disclosure relates to chimeras comprising a stapled peptide conjugated to a compound that binds a protein (e.g., a protein that is involved in or that is causative of disease, e.g., cancer) (e.g., a compound that binds to a BET protein, e.g., JQ1), also referred to herein as Stapled Peptide-PROteolysis Targeting Chimeras (SP-PROTACs), and related compositions and uses thereof, e.g., in the treatment of a disease (e.g., a cancer or other disease driven by or related to the protein to which the compound binds). The chimeras act as combined protein degradation-inducing and protein targeting and moieties, e.g., stapled peptide to recruit the degradation protein such as HDM2 (and target HDMX to maximally reactivate p53) and a small molecule to engage a protein (e.g., a protein that is involved in or that is causative of a disease, e.g., a cancer).

The invention relates to the technical field of polypeptide compounds, in particular to a stapled peptide compound, a preparation method and application thereof and a skin care product. The structural formula of the stapled peptide compound is shown in the specification. The polypeptide has high anti-enzymolysis stability, can significantly improve the expression ability of up-regulated fiber cells and promote the expression of collagen, and can be used in the fields of wrinkle resistance, aging resistance, repair and the like.

The present disclosure provides novel polypeptide conjugates. The polypeptide conjugates disclosed herein comprise a stapled peptide, which comprises a peptide and at least one staple that holds the peptide in an α-helical structure, and a cyclic cell-penetrating peptide (cCPP) conjugated directly or indirectly to the stapled peptide. The present disclosure demonstrates that the cCPP can be used to confer consistent cell permeability to the stapled peptide.

Stapled peptides and mutant BCL-2 family peptides and compositions comprising the same are provided. Also provided are methods of using the stapled peptides and mutant BCL-2 family peptides for selectively protecting sensory neurons from age-related and / or chemotherapy induced axonal degeneration in a human subject in need thereof, treating or preventing chemotherapy induced peripheral neuropathy (CIPN) in a human subject in need thereof, averting neuropathic side effects of chemotherapy and / or other causes of axonal degeneration in a human subject in need thereof, and treating or preventing hearing loss in a human subject in need thereof. The methods involve administering to the human subject a stapled peptide and a mutant BCL-2 family peptide disclosed herein.

Stapled peptides and mutant BCL-2 family peptides and compositions comprising the same are provided. Also provided are methods of using the stapled peptides and mutant BCL-2 family peptides for selectively protecting sensory neurons from age-related and / or chemotherapy induced axonal degeneration in a human subject in need thereof, treating or preventing chemotherapy induced peripheral neuropathy (CIPN) in a human subject in need thereof, averting neuropathic side effects of chemotherapy and / or other causes of axonal degeneration in a human subject in need thereof, and treating or preventing hearing loss in a human subject in need thereof. The methods involve administering to the human subject a stapled peptide and a mutant BCL-2 family peptide disclosed herein.

This disclosure relates to chimeras comprising a stapled peptide conjugated to a compound that binds a protein (e.g., a protein that is involved in or that is causative of disease, e.g., cancer) (e.g., a compound that binds to a BET protein, e.g., JQ1), also referred to herein as Stapled Peptide-PROteolysis Targeting Chimeras (SP-PROTACs), and related compositions and uses thereof, e.g., in the treatment of a disease (e.g., a cancer or other disease driven by or related to the protein to which the compound binds). The chimeras act as combined protein degradation-inducing and protein targeting and moieties, e.g., stapled peptide to recruit the degradation protein such as HDM2 (and target HDMX to maximally reactivate p53) and a small molecule to engage a protein (e.g., a protein that is involved in or that is causative of a disease, e.g., a cancer).

Stapled BAD BH3 peptides and compositions comprising the same that are useful in overcoming venetoclax resistance are provided. Also provided are methods of using the stapled BAD BH3 peptides for treating a BCL-2 expressing and / or dependent cancer (e.g., a hematologic cancer or a solid tumor) in a human subject in need thereof. In some cases, the cancer is a venetoclax-resistant cancer due to acquired mutations in the BCL-2 protein. The methods involve administering to the human subject a stapled BAD BH3 peptide or pharmaceutical composition or delivery vehicle comprising the stapled BAD BH3 peptide disclosed herein.

The application belongs to the field of polypeptide drugs, and particularly relates to an antibacterial polypeptide and application thereof. The Rink amide MBHA amino resin is used as a solid phase carrier, and a template polypeptide raniseptin PL: Ac-GVFDTVKKIGKAVGKFALGVAKNYLNS-NH2 amino acid sequence is modified and reformed. On the basis of reserving key amino acid residues, S5 and R8 are respectively used to replace original amino acids at i, i+4 and i, i+7 amino acid positions, so that a target stapled peptide is obtained. The stapled peptide can significantly improve the antibacterial activity on Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis and Staphylococcus epidermidis relative to the template polypeptide PL-0.

This invention discloses a stapled peptide, its preparation method, and its applications. The method involves using an amino resin as a solid-phase support, synthesizing a peptide chain in a condensation system according to the linear peptide template LNWGAILKHIIK-NH2 via Fmoc solid-phase synthesis. While retaining key amino acid residues, S5 is used to replace the original amino acid at positions i and i+4, where i = 1-7, resulting in a linear peptide linked to the resin. This linear peptide undergoes an olefin metathesis reaction under the catalysis of Grubbs I reagent, followed by cyclization and cleavage from the resin to obtain the target stapled peptide. This method is simple and easy to implement, yielding a stapled peptide with a purity greater than 95% and a high yield. The synthesized stapled peptide significantly improves protein hydrolysis stability and cell membrane permeability, and can significantly inhibit the growth and proliferation of human breast cancer cells and human liver cancer cells, showing potential application value in the treatment of tumor diseases.

The present invention provides stapled polypeptides of the Formulae (I) and (VI):and salts thereof; wherein the groups ; R1a, R1b, R1c, R2a, R3a, R2b, R3b, R4a, R4b, RA, RZ, L1a, L1b, L2, L3, XAA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

Among other things, the present disclosure provides various useful agents. In some embodiments, provided agents can bind to beta-catenin. In some embodiments, the present disclosure provides technologies for modulating beta-catenin levels in a system. In some embodiments, the present disclosure provides technologies for modulating beta-catenin functions. In some embodiments, the present disclosure provides technologies for preventing and / or treating conditions, disorders or diseases associated with beta-catenin.