Triple agonists of GLP1 / GIP / NPY2 receptor

Abstract

Disclosed are hybrid polypeptides that agonize GIP, GLP-1 and neuropeptide Y2 (NPY2) receptors and their medical use in the treatment of a variety of diseases, conditions or conditions, such as obesity, diabetes and / or NASH. The polypeptides have the general structure Z1-Z2-Z3 wherein Z1 is a hybrid polypeptide that provides GIPR and GLP1R agonism, Z2 is a linker, and Z3 is a polypeptide that provides hY2R agonism.

Description

Technical Field

[0001] The present invention relates to hybrid polypeptides that agonize GIP, GLP-1 and neuropeptide Y2 (NPY2) receptors and their medical use in the treatment of various diseases, conditions or disorders such as obesity, diabetes and / or NASH. Prior Art

[0002] Overweight and obesity are defined as abnormal or excessive fat accumulation that poses a risk to health. A body mass index (BMI) above 27 kg / m 2 is considered overweight, and a BMI above 30 kg / m 2 is considered obese. BMI is calculated based on weight and height. Over the past 50 years, obesity has reached pandemic levels. Since 1975, the global obesity rate has almost tripled. In 2016, more than 1.9 billion adults and more than 340 million children and adolescents were overweight or obese. Overweight and obesity are major risk factors for many chronic diseases, including type 2 diabetes, cardiovascular disease and cancer, which are the leading causes of morbidity and mortality in the United States. Thus, obesity is a serious condition and is associated with poor mental health, reduced quality of life, and a decrease in life expectancy (Abdelaal 2017). According to the WHO, overweight and obesity are no longer considered problems exclusive to high-income countries and are rising sharply in low- and middle-income countries. The WHO Global Health Observatory indicates that in 2016, 39% of women or men aged 18 and over were overweight and 11% of men and 15% of women were obese.

[0003] Peptide YY (PYY) is a 36-amino acid peptide with the sequence YPIKPEAPREDASPEELNRYYA SLRHYLNLVTRQRY (SEQ ID NO:308), which is found in the mucosa of the gastrointestinal tract, particularly in endocrine L cells in the ileum and colon. PYY, together with neuropeptide Y (NPY) and pancreatic polypeptide (PP), belongs to the pancreatic polypeptide (PP) family. This peptide family acts on NPY receptors named NPY1R (Y1), NPY2R (Y2), NPY4R (Y4) and NPY5R (Y5). The receptor family belongs to a class of G protein-coupled receptors (GPCRs) expressed in the CNS, particularly in regions of the hypothalamus. The receptors NPY1R-NPY5R exhibit anorectic effects (NPY2R, NPY4R) and orexigenic effects (NPY5R, NPY1R). The two main forms of peptide YY are PYY 1-36 and PYY 3-36 . PYY 1-36 is released from intestinal L cells in proportion to energy intake after a meal and is partially truncated to PYY 3-36 , which PYY 3-36It is the main circulating form of PYY and a relatively selective Y2 receptor agonist. PYY 1-36 and PYY 3-36 inhibit gastric acid secretion, gastrointestinal transit, and food intake. Food intake is inhibited via the stimulation of Y2 receptors on vagal afferent neurons and the interaction with Y2 receptors in the hypothalamus, which is consistent with the ability of PYY to enter the brain via circumventricular organs (such as the area postrema and subfornical organ). In addition, the concentration of PYY in the blood of obese individuals is known to be lower than that of healthy individuals. Therefore, NPY2R and / or NPY4R agonists may have potential in the treatment of obesity.

[0004] Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) belong to the incretin family. GLP-1(7-37) is a 31-amino acid peptide with the sequence HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG (SEQ ID NO: 309), and GIP is a 42-amino acid peptide with the sequence YAEGTFISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQ (SEQ ID NO: 310). GLP-1 and GIP are secreted from intestinal L cells and K cells, respectively. GLP-1 acts via the GLP-1 receptor and is known to have glucose-dependent insulinotropic effects (i.e., stimulating insulin release) and anorectic effects. GIP acts via the GIP receptor and is also known to have glucose-dependent insulinotropic effects, but its effect on food intake is unclear. GLP-1 receptor / GIP receptor co-agonist peptides have been reported to exhibit stronger hypoglycemic and weight loss effects than GLP-1 receptor agonists alone. Therefore, studies have been conducted based on the structures of native glucagon, GIP, or GLP-1 to develop GLP-1 / GIP receptor co-agonists for the treatment of obesity and / or diabetes.

[0005] The most notable effect of GLP-1 agonists is their ability to promote insulin secretion in a glucose-dependent manner by binding to the GLP-1 receptor expressed on pancreatic β-cells. Almost equally important, GLP-1 agonists have been shown to inhibit glucagon secretion at glucose levels above fasting levels. Decisively, this does not affect the glucagon response to hypoglycemia, making GLP-1 agonists a safe anti-diabetic drug with a very low incidence of hypoglycemia compared to insulin. In June 2021, Semaglutide, a GLP-1 agonist, was approved by the FDA for long-term weight management in obese or overweight adults with at least one weight-related condition such as hypertension, type 2 diabetes, or high cholesterol. As an anti-obesity drug, GLP-1 agonists act by binding to GLP-1 receptors in the hypothalamus, thereby suppressing appetite. In addition, GLP-1 agonists bind to GLP-1 receptors in the stomach, inhibiting gastric emptying, gastric acid secretion, and peristalsis, which together promote satiety. Thus, diabetic individuals treated with GLP-1 receptor agonists typically also experience beneficial weight loss in addition to controlling their blood glucose levels.

[0006] However, despite long-term efforts, the number of overweight and obese patients is still growing. First-line therapies for overweight and obese patients include diet and exercise, but are often not sufficiently effective. Second-line treatment options are bariatric surgery and drug therapy. Existing drug therapies appear to lack efficacy and / or safety, and there are only a limited number of approved therapies in the United States and Europe, such as Semaglutide. Thus, there remains a high medical need for more effective and safer treatment options. Given the biological roles of PYY, GIP, or GLP-1, future obesity treatments may benefit from simultaneously targeting GLP1-R, GIPR, and NPY2R. Indeed, recent research efforts in the obesity field aim to develop hybrid polypeptides that are triple agonists of these receptors (see, for example, EP3467106 A1). For several reasons, hybrid polypeptides are highly desirable compared to combination therapies using individual polypeptides. First, hybrid polypeptides are easier to formulate into a single dosage unit compared to mixtures of different polypeptides. This is mainly because different peptides can have different physicochemical properties at a given pH, such as isoelectric point, solubility, or chemical stability, meaning that a formulation developed for one polypeptide may not be ideal or compatible for another polypeptide. Thus, combination therapies using individual polypeptides may require individual dosage units. Second, hybrid polypeptides are cheaper to manufacture and also reduce the burden of regulatory approval compared to individual polypeptides.

[0007] The present invention sets out to provide hybrid polypeptides that agonize all receptors GLP1-R, GIPR, and NPY2R in order to provide improved treatment of, for example, obesity, diabetes, and / or metabolic syndrome.

[0008] In addition, an object of the present invention is to provide a triple agonist that is soluble at or about physiological pH (e.g., pH 7).

[0009] Another object of the present invention is to provide a triple agonist that has a long duration of action in vivo, i.e., a long in vivo half-life.

[0010] Another object of the present invention is to provide a triple agonist that activates all receptors GLP1-R, GIPR, and NPY2R and is soluble at or about physiological pH (e.g., pH 7).

[0011] Another object of the present invention is to provide a triple agonist that activates all receptors GLP1-R, GIPR, and NPY2R, is soluble at or about physiological pH (e.g., pH 7), and has a long duration of action in vivo.

[0012] Another object of the present invention is to provide a triple agonist that exhibits good selectivity for the GLP-1, GIP, and NPY2 receptors relative to other incretins or related receptors. For example, the agonists of the present invention may not activate other receptors from the NPY receptor family, such as the NPY1, NPY4, or NPY5 receptors, and / or may not activate the GLP-2 or glucagon receptors. SUMMARY OF THE INVENTION

[0013] In a first aspect, the present invention provides a polypeptide of general structure according to formula (I) or a pharmaceutically acceptable salt thereof. Z1-Z2-Z3 (I), wherein, Z1 is a heteromeric polypeptide that provides GIPR and GLP1R agonistic effects and comprises the following amino acid sequence, Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO: 306), or a derivative thereof having 1, 2, or 3 substitutions; Z2 is a linker; Z3 is a polypeptide that provides hY2R agonistic effects and comprises the following amino acid sequence, A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO: 307) or a derivative thereof having 1, 2, 3, 4, or 5 substitutions.

[0014] In a second aspect, the present invention provides a polypeptide of general structure according to formula (I) or a pharmaceutically acceptable salt thereof, Z1-Z2-Z3(SEQ ID NO:647) (I), wherein, Z1 is a GIP / GLP1 hybrid polypeptide comprising the following amino acid sequence, Y-Aib-X3-G-T-F-T-S-D-X 10 -S-I-X 13 -L-X 15 -X 16 -X 17 -A-X 19 -X 20 -X 21 -F-X 23 -X 24 -X 25 -L-X 27 -K(SEQ ID NO:646), wherein X3 is selected to be E or D; X 10 is selected to be Y or L; X 13 is selected to be Aib or L; X 15 is selected to be E, D or A; X 16 is selected to be K, E, D, Aib, G, LysAc, A, L, S, Q or R; X 17 is selected to be Q, E, K or A; X 19 is selected to be Q or E; X 20 is selected to be Aib, D-Asp or D-Arg; X 21 is selected to be A, E or K; X 23 is selected to be V or I; X 24 is selected to be E or Q; X 25 is selected to be W or Y; X 27 is I or L; Z2 is a linker composed of the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 ; wherein X 31 is selected to be P, G or Q; X 32 is selected to be S, E or R; X 33 is selected to be S, E, Y or T; X 34 is selected to be G, P, Y or A; Z3 is a polypeptide comprising the following amino acid sequence, X 35 -X 36 -X 37 -X 38 -X 39 -Y-X41 -X 42 -X 43 -X 44 -T-X 46 -X 47 -X 48 -X 49 , wherein X 35 is selected from A, Q, I, V, E or L; X 36 is selected from S, E, T, D or L; X 37 is selected from L, Aib, V, D-Leu, I or Tle; X 38 is selected from R, L or Aib; X 39 is selected from H, Aib, D-His or Tle; X 41 is selected from L, Y, Aib, I or Tle; X 42 is selected from N or Aib; X 43 is selected from W, H, L, R or Aib; X 44 is selected from L, Aib, D-Arg, D-Asp or Tle; X 46 is selected from R, hArg or D-Arg; X 47 is selected from Q, bh-Gln or NMeQ; X 48 is selected from R or NMeR; X 49 is selected from Y, Tle, Chg, D-Tyr, Phg.

[0015] In a third aspect, the invention relates to a polypeptide according to the first or second aspect, which is used as a medicament.

[0016] In a fourth aspect, the invention relates to a method for treating a disease, disorder and / or condition selected from the list consisting of: overweight, obesity, type 1 and type 2 diabetes, eating disorders, hyperlipidemia, metabolic syndrome, NAFLD / NASH and / or cardiovascular diseases, the method comprising administering to an individual in need a therapeutically effective amount of a polypeptide according to the first or second aspect or a pharmaceutically acceptable salt thereof.

[0017] Terms, definitions and conventions Terms not specifically defined herein shall be given the meaning that would be given to them by a person skilled in the art in view of the disclosure and the context. However, unless otherwise specified, the following terms, as used in this specification, have the specified meanings and the following conventions shall be observed.

[0018] Amino acid According to the present invention, unless otherwise specified, amino acids are L-amino acids (L-stereoisomers, natural amino acids). In the present context, substitutions in analogs / derivatives can be substitutions for natural amino acids as well as non-natural amino acids (including L-stereoisomers and D-stereoisomers). Substitutions in derivatives can be conservative substitutions with conservative amino acids. The groups of conservative amino acids can be defined as: G, A, V, L, I, P (aliphatic or cyclic), S, C, T, M (containing a hydroxyl or sulfur) F, Y, W (aromatic) H, K, R (basic) D, E, N, Q (acidic or amide)

[0019] Common non-natural amino acids include NMeG, which represents the amino acid methylglycine (also known as N-methylglycine, NMeGly, MeGly or sarcosine); NMeP, which represents the amino acid methyl-L-proline (also known as N-methyl-L-proline, NMePro or (S)-1-methylpyrrolidine-2-carboxylic acid); Dpr, which represents the amino acid (S)-2,3-diaminopropionic acid (also known as L-2,3-diaminopropionic acid); Aib, which represents the amino acid 2-amino-2-methylpropionic acid (also known as 2-aminoisobutyric acid); NMeQ, which represents the amino acid N-methyl-L-glutamine (also known as N-methylglutamine, NMeGln or MeGln); NMeAla, which represents the amino acid N-methyl-L-alanine (also known as N-methylalanine, NMeA or MeAla); Cha, which represents the amino acid (S)-2-amino-3-cyclohexylpropionic acid (also known as L-cyclohexylalanine); Tle, which represents the amino acid (S)-2-amino-3,3-dimethylbutyric acid (also known as L-2-(tert-butyl)glycine); 1-Nal represents the amino acid (S)-2-amino-3-(naphthalen-1-yl)propionic acid (also known as 3-(1-naphthyl)-L-alanine); Pip, which represents the amino acid (S)-piperidine-2-carboxylic acid (also known as L-pipecolic acid); Nip, which represents the amino acid (S)-piperidine-3-carboxylic acid (also known as L-pipecolic acid); Nle, which represents the amino acid (2S)-2-aminohexanoic acid (also known as L-norleucine); Phe(4F), which represents the amino acid (S)-2-amino-3-(4-fluorophenyl)propionic acid (also known as 4-fluoro-L-phenylalanine).

[0020] Salts and pharmaceutically acceptable salts According to the present invention, the polypeptide or its derivative can be in the form of a salt.

[0021] According to the present invention, the polypeptide or its derivative may be in the form of a pharmaceutically acceptable salt. Accordingly, pharmaceutically acceptable salts are intended to include any salts commonly used in the formulation of peptides. Such salts include acid addition salts and basic salts, and examples can be found, for example, in Remington's pharmaceutical sciences, 17th edition. Similarly, the polypeptide or pharmaceutically acceptable salt may be in the form of a solvate (such as a hydrate).

[0022] Nomenclature of compounds: Compounds are represented in the Boehringer Ingelheim Line Notation (BILN), which describes complex peptides in a human-readable format (Fox et al., J. Chem. Inf. Model. 2022, 62, 17, 3942-3947). In the BILN, the chain is composed of monomers, for example, A represents alanine, Aib represents isobutyric acid, and two monomers are connected by a hyphen "-". Different chains are separated by a dot ".", and the connections between the chains are clearly defined in parentheses after the monomers, which include the linkage ID number and the R-group number. For example, K(1,3) represents a lysine residue that is connected to another monomer with the same linkage ID "1" through its R "3"-group (ε-amino group). As an example, Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-L-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:412), where C20DA represents 19-carboxynonadecanoyl, gGlu([γE]) represents L-γ-glutamyl, which is connected to C20DA through its amino group and to the amino group of the next gGlu through its γ-carboxyl group, this is repeated 4 times, resulting in a total of 6 gGlu residues, which are connected to the ε-amino group of lysine (eLys) through the last γ-carboxyl group and to the ε-amino group of lysine (K) in the peptide backbone through the carboxyl group, fully defining the following structure: Structure disclosed as SEQ ID NO:412

[0023] Lipidation As used herein, lipidation refers to optionally through a linker / spacer (-(Y-) 1-8)Covalently link a lipid (L), such as C18DA (octadecanedioic acid), C20DA (eicosanedioic acid), or other half-life extending moiety, to the hybrid polypeptide according to the present invention. The linker / spacer can consist of one or more covalently linked monomers commonly used in the art, such as [γE], [OEG], or [AHX] as illustrated below.

[0024] Lipidation can be carried out at lysine residues in the polypeptide (i.e., at the ε (epsilon) amino group) or at the N-terminus, preferably at lysine residues as exemplified herein. Without wishing to be bound by any theory, it is believed that such lipophilic substituents bind to albumin and other plasma components in the bloodstream, thereby protecting the compounds of the present invention from renal filtration and enzymatic degradation. Thus, lipidation is generally carried out to improve the pharmacokinetic profile of the polypeptide, for example, by modifying metabolic stability, reducing enzymatic degradation, decreasing secretion and metabolism, all of which can result in an extended in vivo half-life (t 1 / 2 ). The polypeptides according to the present invention can be lipidated or non-lipidated depending on the desired half-life. If a linker / spacer is present, the lipid (L) is covalently linked to the linker / spacer at one end (-(Y-) 1-8 ), and the polypeptide is covalently linked to the linker / spacer at the other end (-(Y-) 1-8 )(i.e., lipid-linker-peptide). Alternatively, when no linker / spacer is present, the lipid (L) is directly covalently linked to the polypeptide (i.e., lipid-polypeptide). The linker / spacer can consist of 1 to 8 and including 8 covalently linked monomers (i.e., -Y 1 -; -Y 1 -Y 2 -; -Y 1 -Y 2 -Y 3 -; -Y 1 -Y 2 -Y 3 -Y 4 -; -Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -; -Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -; -Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y7 -; or -Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 -), wherein each unit is independently selected from, for example, [γE], [OEG] or [AHX], or selected from, for example, [γE], [E], [OEG], [eLys] or [AHX]. Most preferably, the polypeptide has the general formula L-Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 - is structurally esterified, wherein L is a lipid selected from C18DA or C20DA, and further wherein Y 1 -Y 8 each of which is independently selected from absent, [γE], [OEG], [eLys] or [AHX], or selected from absent, [γE], [E], [OEG], [eLys] or [AHX].

[0025] The lipid (L) can be linked to the linker / spacer (-(Y-) 1-8 ) via an ester, ether, sulfonyl ester, thioester, amide, amine, triazole or sulfonamide, preferably via an amide or ester linkage. Thus, it should be understood that the lipid (L) preferably comprises an acyl group, a sulfonyl group, an alkyne, an azide, an N atom, an O atom or an S atom, which forms part of an ester, sulfonyl ester, thioester, triazole, amide, amine or sulfonamide. Preferably, the acyl group or O or N atom in the lipophilic substituent (L) forms part of an amide or ester with the linker / spacer (-(Y-) 1-8 )

[0026] Similarly, the linker / spacer (-(Y-) 1-8 )(if present) is linked to the amino acid residue of the hybrid polypeptide according to the invention via an ester, sulfonyl ester, thioester, amide, amine or sulfonamide. Thus, it should be understood that the linker / spacer (if present) preferably comprises an acyl group, a sulfonyl group, an N atom, an O atom or an S atom, which forms part of an ester, sulfonyl ester, thioester, amide, amine or sulfonamide. Preferably, the acyl group or O or N atom in the linker (-(Y-) 1-8 ) forms part of an amide or ester with the amino acid residue.

[0027] The lipophilic substituent (L) may comprise a hydrocarbon chain having from 10 to 24 carbon atoms, such as from 14 to 22 carbon atoms, such as from 16 to 20 carbon atoms. Preferably, it has at least 14 carbon atoms and preferably 20 carbon atoms or less. For example, the hydrocarbon chain may contain 14, 15, 16, 17, 18, 19 or 20 carbon atoms. The hydrocarbon chain may be straight or branched and may be saturated or unsaturated. In addition, the hydrocarbon chain may include a functional group at the end of the hydrocarbon chain, such as a carboxylic acid group, a sulfonic acid group or a tetrazolyl group. In accordance with the foregoing discussion, it should also be understood that the hydrocarbon chain is preferably partially substituted, and this part forms an amino acid residue of the hybrid polypeptide according to the present invention or a linking group (-(Y-) 1-8)(e.g., an acyl group, a sulfonyl group, an N atom, an O atom, or an S atom). Most preferably, the hydrocarbon chain is substituted with an acyl group (for attachment to the linker / spacer), and thus the hydrocarbon chain can be part of an alkanoyl group (e.g., dodecanoyl, 2-butyloctanoyl, tetradecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, or eicosanoyl). These hydrocarbon chains substituted with an acyl group at one end can be further functionalized with a carboxylic acid group at the other end of the chain. Examples of the functionalized hydrocarbon chains (e.g., lipophilic substituent L) are 15-carboxy-pentadecanoyl (abbreviated C16DA), 17-carboxy-heptadecanoyl (abbreviated C18DA), and 19-carboxy-nonadecanoyl (abbreviated C20DA). Preferred lipids or lipid / linkers in the present invention are C18DA, C18DA[E][E][E][E]-(SEQ ID NO:640), C18DA[E][E][E][E][E]-(SEQ ID NO:636), C18DA[E][E][E][E][E][E]-(SEQ ID NO:637), C18DA[γE]-, C18DA[γE][γE]-, C18DA[γE][γE][γE]-, C18DA[γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE][γE][γE]-, C20DA, C20DA[γE]-, C20DA[γE][γE]-, C20DA[γE][γE][γE]-, C20DA[γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE][γE]-, C18DA[eLys], C18DA[E][E][E][E][E][eLys]-(SEQ ID NO:635), C18DA[E][E][E][E][E][E][eLys]-(SEQ ID NO:643), C18DA[γE][eLys]-, C18DA[γE][γE][eLys]-, C18DA[γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][γE][γE][eLys]-, C20DA[eLys]C20DA[E][E][E][E][E][eLys]-(SEQ ID NO:639), C20DA[γE][eLys]-, C20DA[γE][γE][eLys]-, C20DA[γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][eLys][eLys]-, C18DA[OEG][OEG]-, C18DA[E][E][E][OEG][OEG]-, C18DA[E][E][E][E][OEG][OEG]-(SEQ ID NO:634), C18DA[γE][OEG][OEG]-, C18DA[γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][γE][γE][OEG][OEG]-, C20DA[OEG][OEG]-, C20DA[E][E][E][E][OEG][OEG]-(SEQ ID NO:638), C20DA[γE][OEG][OEG]-, C20DA[γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG][OEG]-, C18DA[OEG]-, C18DA[γE][OEG]-, C18DA[γE][γE][OEG]-, C18DA[γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][γE][γE][OEG]-, C20DA[OEG]-, C20DA[γE][OEG]-, C20DA[γE][γE][OEG]-, C20DA[γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][OEG]-,C20DA[γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][γE][OEG]-, C18DA[OEG][eLys]-, C18DA[γE][OEG][eLys]-, C18DA[γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][γE][γE][OEG][eLys]-, C20DA[OEG][eLys]-, C20DA[γE][OEG][eLys]-, C20DA[γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][γE][OEG][eLys]-, C18DA[OEG][OEG][eLys]-, C18DA[γE][OEG][OEG][eLys]-, C18DA[γE][γE][OEG][OEG][eLys]-, C18DA[γE][γE][γE][OEG][OEG][eLys]-, C18DA[γE][γE][γE][γE][OEG][OEG][eLys]-, C20DA[OEG][OEG][eLys]-, C20DA[γE][OEG][OEG][eLys]-, C20DA[γE][γE][OEG][OEG][eLys]-, C20DA[γE][γE][γE][OEG][OEG][eLys]-, C20DA[γE][γE][γE][γE][OEG][OEG][eLys]-, C18DA[AHX], C18DA[γE][AHX]-, C18DA[γE][γE][AHX]-, C18DA[γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][γE][AHX]-, C20DA[AHX], C20DA[γE][AHX]-, C20DA[γE][γE][AHX]-, C20DA[γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][AHX]-,C20DA[γE][γE][γE][γE][γE][AHX]- or C20DA[γE][γE][γE][γE][γE][γE][AHX]-. Preferably, the polypeptide is lipidated at the lysine (K) residue at amino acid position X, 28 in the

[0028] N-terminus and C-terminus In the present invention, the polypeptide is generally amidated at the C-terminus (-CONH2), like a natural peptide. However, the polypeptides of the present invention may also have a free carboxylic acid (-COOH) or another post-translational modification, such as a methyl ester (-COOMe). In a highly preferred embodiment of the present invention, the polypeptide is amidated at the C-terminus. The polypeptides according to the present invention may have a free amine (-NH2), be N-acylated (-NHCOR), N-methylated (-NHCH3 or -N(CH3)2), deaminated at the N-terminus, or N-lipidated.

[0029] Pharmaceutical composition In the present invention, it should be understood that the polypeptide according to the present invention or a pharmaceutically acceptable salt thereof may be in the form of a pharmaceutical composition. The pharmaceutical composition may comprise a pharmaceutically acceptable carrier and / or one or more excipients. Pharmaceutical compositions (i.e., formulations) include (but are not limited to) tablets, pills, capsules, emulsions, suspensions, sustained-release formulations, solutions, or lyophilized powders intended to be dissolved before administration. In some embodiments, the formulation may be a depot formulation that provides slow release. It should be understood that depending on the choice of formulation and the chemical and / or metabolic stability of the polypeptide, different routes of administration may be used. Such routes of administration may include (but are not limited to) oral administration, parenteral administration (intravenous (IV), subcutaneous (SC), intradermal (ID), and intramuscular (IM)), or inhalation. In a preferred embodiment of the present invention, the route of administration is parenteral administration. In an even more preferred embodiment, the route of administration is subcutaneous.

[0030] Peptide therapeutics are typically provided as pharmaceutical liquid formulations in pre-filled ready-to-use injection devices. These peptide formulations for subcutaneous administration have a limited volume of administration. Therefore, it is a requirement for application in ready-to-use injection devices that the peptide has good solubility at or around physiological pH (e.g., pH 7). Detailed description of the invention

[0031] In a first aspect, the present invention provides a polypeptide having the general structure according to formula (I) or a salt or pharmaceutically acceptable salt thereof, Z1-Z2-Z3 (I), wherein, Z1 is a GIP / GLP1 hybrid polypeptide comprising or consisting of the following amino acid sequence, Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(SEQ ID NO:306), or a derivative thereof having 1, 2 or 3 amino acid substitutions; Z2 is a linker; Z3 is a polypeptide comprising or consisting of the following amino acid sequence, A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y(SEQ ID NO:307) or a derivative thereof having 1, 2, 3, 4 or 5 amino acid substitutions.

[0032] The compounds of the present invention bind to and / or activate GLP-1, GIP and hY2 (NPY2) receptors.

[0033] Linker Z2 The peptide fragments Z1 and Z3 are linked through the linker Z2. It should be understood that Z1 and Z3 can be linked through various linkers commonly used in techniques such as fusion proteins. Preferably, the linker comprises a short peptide consisting of 1 to 10 amino acid residues, such as 2 to 9 amino acids, preferably 3 to 8 amino acids, more preferably 4 to 7 amino acids, even more preferably 5 to 7 amino acids, and most preferably 6 amino acid residues, or consists of such a short peptide. Thus, in a preferred embodiment, the linker Z2 consists of 6 amino acid residues (i.e., amino acid X 29 -X 34 ). In a more preferred embodiment, Z2 has or comprises the amino acid sequence GGPSEG (SEQ ID NO:311, i.e., amino acid X 29 -X 34 ) or a derivative thereof having 1, 2, 3 or 4 amino acid substitutions. Preferably, the 1, 2, 3 or 4 amino acid substitutions in Z2 are present at any position in position X 31 , X 32 , X 33 or X 34 (i.e., in the amino acid sequence PSEG (SEQ ID NO:644)). Thus, the Z2 derivative is a Z2 peptide analogue of the amino acid sequence SEQ ID NO:311 having one or more amino acid substitutions compared to SEQ ID NO:311.

[0034] In a highly preferred embodiment (Z2-Emb1), Z2 (i.e., amino acid X 29 -X 34 ) has or comprises the amino acid sequence GGX 31 X 32 X 33 X34 , wherein X 31 is selected from P, G or Q; X 32 is selected from S, E or R; X 33 is selected from S, E or Y, or preferably is selected from S, E, Y or T; X 34 is selected from G, P, Y or A; or is a derivative thereof having 1 amino acid substitution.

[0035] In other highly preferred embodiments, Z2 has the amino acid sequence of any one of the Z2 embodiments disclosed below in the second aspect of the present invention (e.g., Z2-Emb2, Z2-Emb3).

[0036] Heteromeric polypeptide Z1 Z1 (i.e., amino acids X1-X 28 ) is a GIP / GLP1 heteromeric polypeptide that comprises or consists of the amino acid sequence Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO:306), or is a derivative thereof having 1, 2 or 3 amino acid substitutions. The sequence Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO:306) (i.e., Z1 in SEQ ID NO:286) is selected as the reference sequence. Table 1 outlines (see page 21ff) the number of substitutions in Z1, one or more positions of substituted Z1, and the exemplary amino acids in the substitutions compared to the reference sequence (i.e., SEQ ID NO:286). As shown in Table 1, it was found that amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 23 , X 24 , X 25 or X 27 are tolerant to substitution. Thus, in a preferred embodiment, 1, 2 or 3 substitutions in the derivative of Z1 are present at amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 23 , X24 , X 25 or X 27 at any position. Preferably, the derivative of Z1 has 1 or 2 substitutions. Most preferably, the derivative of Z1 has 1 substitution. Thus, the Z1 derivative is a Z1 peptide analogue of the amino acid sequence SEQ ID NO: 306 having one or more amino acid substitutions as compared to SEQ ID NO: 306 (i.e., Z1 in SEQ ID NO: 286).

[0037] In a highly preferred embodiment, one or more of the substitutions in the derivative of Z1 are selected as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D or A; X 16 is selected as E, D, Aib, G, LysAc, A, L, S, Q or R; X 17 is selected as E, K or A; X 19 is selected as E; X 20 is selected as D-Asp or D-Arg; X 21 is selected as E, or preferably is selected as E or K; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y; X 27 is selected as L.

[0038] Z1 may consist of or comprise the amino acid sequence Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO: 306), or may be a derivative thereof, the derivative having 1, 2 or 3 amino acid substitutions at any position of amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 21 , X 23 , X 24 , X 25 or X 27 wherein one or more of the substitutions are selected as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D; X 16 is selected as E, D, G, A, S, Q or R; X 17 is selected as E or A; X19 Selected as E; X 21 Selected as E or K; X 23 Selected as I; X 24 Selected as Q; X 25 Selected as Y; X 27 Selected as L.

[0039] Z1 may consist of or contain the amino acid sequence Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K (SEQ ID NO:306), or may be a derivative thereof, and the derivative has 1, 2 or 3 amino acid substitutions at any position among amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 21 , X 23 , X 24 or X 25 wherein the substitution selections are as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D; X 16 is selected as E, D, G, A, S, Q or R; X 17 is selected as E or A; X 21 is selected as E; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y.

[0040] Z1 may consist of or contain the amino acid sequence Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K (SEQ ID NO:306), or may be a derivative thereof, and the derivative has 1 or 2, preferably 1 amino acid substitution at any position among amino acid positions X 21 or X 24 wherein one or more substitution selections are as follows: X 21 is selected as A or E; X 24 is selected as E or Q.

[0041] Polypeptide Z3 Z3 (i.e., amino acid X 35 -X 49)Polypeptides providing hY2R agonistic activity, which comprise the amino acid sequence A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO: 307) or consist thereof, or are derivatives thereof having 1, 2, 3, 4 or 5 amino acid substitutions. The sequence A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO: 307) (i.e., Z3 in SEQ ID NO: 286) was selected as the reference sequence. Table 1 outlines (see page 39ff) the number of substitutions in Z3, the positions in Z3 that can be substituted, and the exemplary amino acids in the substitutions compared to the reference sequence (i.e., SEQ ID NO: 286). As shown in Table 1, it was found that amino acid positions X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 42 , X 43 , X 44 , X 46 , X 47 , X 48 or X 49 are tolerant to substitution. Thus, in a preferred embodiment, 1, 2, 3, 4 or 5 substitutions in the derivative of Z3 are present at amino acid positions X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 42 , X 43 , X 44 , X 46 , X 47 , X 48 or X 49 in any of the positions. In a preferred embodiment, Z3 has 1, 2 or 3 substitutions. More preferably, Z3 has 1 or 2 substitutions. Most preferably, Z3 has 1 substitution. Thus, the Z3 derivative is a Z3 peptide mimetic of the amino acid sequence SEQ ID NO: 307 (i.e., Z3 in SEQ ID NO: 286) having one or more amino acid substitutions compared to SEQ ID NO: 307.

[0042] In a highly preferred embodiment, one or more substitutions in the derivative of Z3 are selected as follows: X 35 is selected as Q, I, V, E or L; X 36 is selected as E, T, D or L; X 37is selected from Aib, V, D-Leu or I, or preferably is selected from Aib, V, D-Leu, I or Tle; X 38 Selected as L or Aib; X 39 Selected as Aib, D-His or Tle; X 41 Selected as L, Aib, I or Tle; X 42 Selected as Aib;X 43 Selected as H, L, R or Aib; X 44 is selected as Aib, D-Arg or D-Asp, or preferably is selected as Aib, D-Arg, D-Asp or Tle; X 46 Selected to be hArg or D-Arg; X 47 Selected as bh-Gln or NMeQ; X 48 Selected as NMeR; X 49 Selected are Tle, Chg, D-Tyr, Phg.

[0043] Z3 may consist of or comprise the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or may be a derivative thereof, wherein at amino acid position X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 44 , X 47 or X 48 Any position in has 1, 2 or 3 amino acid substitutions, wherein one or more substitutions are selected from the following: X 35 Selected as Q, I, V, E or L; X 36 Selected as T; X 37 Selected as Aib, V, I or Tle; X 38 Selected as Aib;X 39 Selected as Tle; X 41 Selected as I, L or Tle; X 44 Selected as Tle; X 47 Selected as NMeQ; X 48 Selected is NMeR.

[0044] Z3 may consist of or comprise the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or may be a derivative thereof, wherein at amino acid position X 35 , X 37 , X47 or X 48 has 1 or 2, preferably 1 amino acid substitution at any position in 48 , wherein one or more of the substitutions are selected as follows: X 35 is selected as Q, V; X 37 is selected as I; X 47 is selected as NMeQ; X 48 is selected as NMeR.

[0045] Generally speaking, compared with SEQ ID NO:286, the polypeptide Z1-Z2-Z3 according to the first aspect of the present invention and according to any one or more of the embodiments disclosed in the present invention preferably has 0, 1, 2, 3, 4, 5 or 6 amino acid substitutions, more preferably 0, 1, 2, 3 or 4 amino acid substitutions, and highly preferably 0, 1, 2 or 3 substitutions.

[0046] In a second aspect, the present invention provides a polypeptide having the general structure according to formula (I) or a salt or pharmaceutically acceptable salt thereof, Z1-Z2-Z3(SEQ ID NO:647) (I), wherein, Z1 is a GIP / GLP1 hybrid polypeptide comprising or consisting of the following amino acid sequence, Y-Aib-X3-G-T-F-T-S-D-X 10 -S-I-X 13 -L-X 15 -X 16 -X 17 -A-X 19 -X 20 -X 21 -F-X 23 -X 24 -X 25 -L-X 27 -K(SEQ ID NO:646), wherein X3 is selected as E or D; X 10 is selected as Y or L; X 13 is selected as Aib or L; X 15 is selected as E, D or A; X 16 is selected as K, E, D, Aib, G, LysAc, A, L, S, Q or R; X 17 is selected as Q, E, K or A; X 19 is selected as Q or E; X 20 is selected as Aib, D-Asp or D-Arg; X 21 is selected as A, E or K; X 23 is selected as V or I; X24 Selected as E or Q; X 25 Selected as W or Y; X 27 Is I or L; or Z1 is a derivative thereof having 1 amino acid substitution; Z2 is a linking group comprising the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 or consisting of, wherein X 31 Selected as P, G or Q; X 32 Selected as S, E or R; X 33 Selected as S, E, Y or T; X 34 Selected as G, P, Y or A; or Z2 is a derivative thereof having 1 amino acid substitution.

[0047] Z3 is a polypeptide comprising or consisting of the following amino acid sequence, X 35 -X 36 -X 37 -X 38 -X 39 -Y-X 41 -X 42 -X 43 -X 44 -T-X 46 -X 47 -X 48 -X 49 , wherein X 35 Selected as A, Q, I, V, E or L; X 36 Selected as S, E, T, D or L; X 37 Selected as L, Aib, V, D-Leu, I or Tle; X 38 Selected as R, L or Aib; X 39 Selected as H, Aib, D-His or Tle; X 41 Selected as Y, L, Aib, I or Tle; X 42 Selected as N or Aib; X 43 Selected as W, H, L, R or Aib; X 44 Selected as L, Aib, D-Arg, D-Asp or Tle; X 46 Selected as R, hArg or D-Arg; X 47 Selected as Q, bh-Gln or NMeQ; X 48 Selected as R or NMeR; X 49Selected as Y, Tle, Chg, D-Tyr, Phg; or Z3 is a derivative thereof having 1 amino acid substitution.

[0048] Preferred amino acids in Z1 In a preferred embodiment (Z1-Emb1), X3 is selected as E or D; X 10 Selected as Y or L; X 13 Selected as Aib or L; X 15 Selected as E or D; X 16 Selected as K, E, D, G, A, S, Q or R; X 17 Selected as Q, E or A; X 19 Selected as E or Q; X 20 Selected as Aib; X 21 Selected as A, E or K; X 23 Selected as V or I; X 24 Selected as E or Q; X 25 Selected as W or Y; X 27 Selected as I or L; Or Z1 is a derivative thereof having 1 amino acid substitution;

[0049] In a preferred embodiment (Z1-Emb2), X3 is selected as E or D; X 10 Selected as Y or L; X 13 Selected as Aib or L; X 15 Selected as E or D; X 16 Selected as K, E, D, G, A, S, Q or R; X 17 Selected as Q, E or A; X 19 Selected as Q; X 20 Selected as Aib; X 21 Selected as A or E; X 23 Selected as V or I; X 24Selected to be E or Q; X 25 Selected to be W or Y; X 27 Is I; Or Z1 is a derivative thereof having 1 amino acid substitution;

[0050] In a preferred embodiment (Z1-Emb3), X3 is selected to be E; X 10 Selected to be Y; X 13 Selected to be Aib; X 15 Selected to be E; X 16 Selected to be K; X 17 Selected to be Q; X 19 Selected to be Q; X 20 Selected to be Aib; X 21 Selected to be A or E; X 23 Selected to be V; X 24 Selected to be E or Q; X 25 Selected to be W; X 27 Is I; Or Z1 is a derivative thereof having 1 amino acid substitution.

[0051] In a preferred embodiment, X3 in Z1 is selected to be E. In a preferred embodiment, X in Z1 10 Is selected to be Y. In a preferred embodiment, X in Z1 13 Is selected to be Aib. In a preferred embodiment, X in Z1 15 Is selected to be E. In a preferred embodiment, X in Z1 16 Is selected to be K. In a preferred embodiment, X in Z1 17 Is selected to be Q. In a preferred embodiment, X in Z1 19 Is selected to be Q. In a preferred embodiment, X in Z1 20 Is selected to be Aib. In a preferred embodiment, X in Z1 21 Is selected to be A. In a preferred embodiment, X in Z1 23 Is selected to be V. In a preferred embodiment, X in Z1 24Selected as E. In a preferred embodiment, X in Z1 25 Selected as W. In a preferred embodiment, X in Z1 27 Selected as I.

[0052] In a highly preferred embodiment, X3 in Z1 is selected as E; X in Z1 10 Selected as Y; and X in Z1 13 Selected as Aib. In a highly preferred embodiment, X in Z1 15 Selected as E; X in Z1 16 Selected as K; and X in Z1 17 Selected as Q. In a highly preferred embodiment, X in Z1 19 Selected as Q; X in Z1 20 Selected as Aib; and X in Z1 21 Selected as A. In a highly preferred embodiment, X in Z1 23 Selected as V; X in Z1 24 Selected as E; X in Z1 25 Selected as W; and X in Z1 27 Selected as I.

[0053] Preferred amino acids in Z2 In a preferred embodiment (Z2-Emb1), Z2 comprises the amino acid sequence GGX 31 X 32 X 33 X 34 or consists thereof, wherein X 31 is selected as P, G or Q; X 32 is selected as S, E or R; X 33 is selected as S, E, Y or T; X 34 is selected as G, P, Y or A; or Z2 is a derivative thereof having 1 amino acid substitution.

[0054] In a preferred embodiment (Z2-Emb2), Z2 comprises the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 or consists thereof, wherein X 31 is selected as P or Q; X 32 is selected as S or E; X 33 is selected as S, E, Y or T; X 34 is selected as G, P, Y or A; or Z2 is a derivative thereof having 1 amino acid substitution.

[0055] In a highly preferred embodiment (Z2-Emb3), Z2 comprises or consists of the amino acid sequence GGPSEG (SEQ ID NO:311) or GGPSSG (SEQ ID NO:320); or Z2 is a derivative thereof having 1 amino acid substitution.

[0056] In a preferred embodiment, X in Z2 31 is selected to be P. In a preferred embodiment, X in Z2 32 is selected to be S. In a preferred embodiment, X in Z2 33 is selected to be S. In a preferred embodiment, X in Z2 34 is selected to be G.

[0057] In another embodiment (Z2-Emb4), Z2 is selected from the group consisting of: GGPEEG (SEQ ID NO:313), GGPEEP (SEQ ID NO:314), GGPESG (SEQ ID NO:315), GGPESP (SEQ ID NO:316), GGPSEG (SEQ ID NO:311), GGPSEP (SEQ ID NO:317), GGPSEY (SEQ ID NO:318), GGPSSA (SEQ ID NO:319), GGPSSG (SEQ ID NO:320), GGPSSP (SEQ ID NO:321), GGPSSY (SEQ ID NO:322), GGPSTG (SEQ ID NO:323), GGPSYG (SEQ ID NO:324), GGQSSG (SEQ ID NO:325), GGGSEY (SEQ ID NO:648), GGPEYY (SEQ ID NO:649), GGPRSG (SEQ ID NO:650), GGPRYY (SEQ ID NO:651), GGPSYY (SEQ ID NO:652), GGQRSY (SEQ ID NO:653), GGQRYY (SEQ ID NO:654), GGQSSY (SEQ ID NO:655).

[0058] In another embodiment (Z2-Emb5), Z2 is selected from the group consisting of: GGPEEG (SEQ ID NO:313), GGPEEP (SEQ ID NO:314), GGPESG (SEQ ID NO:315), GGPESP (SEQ ID NO:316), GGPSEG (SEQ ID NO:311), GGPSEP (SEQ ID NO:317), GGPSEY (SEQ ID NO:318), GGPSSA (SEQ ID NO:319), GGPSSG (SEQ ID NO:320), GGPSSP (SEQ ID NO:321), GGPSSY (SEQ ID NO:322), GGPSTG (SEQ ID NO:323), GGPSYG (SEQ ID NO:324), GGQSSG (SEQ ID NO:325), GGPRSG (SEQ ID NO:650), GGPRYY (SEQ ID NO:651), GGPSYY (SEQ ID NO:652).

[0059] In another embodiment (Z2-Emb6), Z2 is selected from the group consisting of: GGPEEG (SEQ ID NO:313), GGPEEP (SEQ ID NO:314), GGPESG (SEQ ID NO:315), GGPESP (SEQ ID NO:316), GGPSEG (SEQ ID NO:311), GGPSEP (SEQ ID NO:317), GGPSEY (SEQ ID NO:318), GGPSSA (SEQ ID NO:319), GGPSSG (SEQ ID NO:320), GGPSSP (SEQ ID NO:321), GGPSSY (SEQ ID NO:322), GGPSTG (SEQ ID NO:323), GGPSYG (SEQ ID NO:324), GGQSSG (SEQ ID NO:325).

[0060] In another embodiment (Z2-Emb7), Z2 is selected from the group consisting of: GGPEEG (SEQ ID NO:313), GGPESG (SEQ ID NO:315), GGPESP (SEQ ID NO:316), GGPSEG (SEQ ID NO:311), GGPSEP (SEQ ID NO:317), GGPSEY (SEQ ID NO:318), GGPSSA (SEQ ID NO:319), GGPSSG (SEQ ID NO:320), GGPSSP (SEQ ID NO:321), GGPSSY (SEQ ID NO:322), GGPSTG (SEQ ID NO:323), GGPSYG (SEQ ID NO:324), GGQSSG (SEQ ID NO:325).

[0061] Preferred amino acids in Z3 In another embodiment (Z3-Emb1), X 35 is selected to be A, E, I, L, Q, and V; X 36 is selected to be S or T; X 37 is selected to be Aib, I, L, Tle, and V; X 38 is selected to be Aib or R; X 39 is selected to be H or Tle; X 41 is selected to be I, L, Tle, or Y; X 42 is selected to be N; X 43 is selected to be W; X 44 is selected to be L or Tle; X 46 is selected to be R; X 47 is selected to be NMeQ or Q; X 48 is selected to be NMeR or R; X 49 is selected to be Y; or Z3 is a derivative thereof having 1 amino acid substitution.

[0062] In a preferred embodiment (Z3-Emb2), X 35 is selected to be A, Q, or V; X 36 is selected to be S; X 37 is selected as I or L; X 38 is selected as R; X 39 is selected as H; X 41 is selected as Y; X 42 is selected as N; X 43 is selected as W; X 44 is selected as L; X 46 is selected as R; X 47 is selected as Q or NMeQ; X 48 is selected as R or NMeR; X 49 is selected as Y; or Z3 is a derivative thereof having 1 amino acid substitution.

[0063] In a preferred embodiment, X in Z3 35 is selected as A. In a preferred embodiment, X in Z3 36 is selected as S. In a preferred embodiment, X in Z3 37 is selected as L. In a preferred embodiment, X in Z3 38 is selected as R. In a preferred embodiment, X in Z3 39 is selected as H. In a preferred embodiment, X in Z3 41 is selected as Y. In a preferred embodiment, X in Z3 42 is selected as N. In a preferred embodiment, X in Z3 43 is selected as W. In a preferred embodiment, X in Z3 44 is selected as L. In a preferred embodiment, X in Z3 46 is selected as R. In a preferred embodiment, X in Z3 47 is selected as Q. In a preferred embodiment, X in Z3 48 is selected as R. In a preferred embodiment, X in Z3 49 is selected as Y.

[0064] In a highly preferred embodiment, X 35 X 36 X 37 X 38 X 39Selected as ASLRH (SEQ ID NO: 645). In a highly preferred embodiment, X 41 X 42 X 43 X 44 Selected as YNWL (SEQ ID NO: 326). In a highly preferred embodiment, X 46 X 47 X 48 X 49 Selected as RQRY (SEQ ID NO: 327).

[0065] It should be understood that the second aspect of the present invention and / or any related embodiments disclosed above and below may be subordinate to the first aspect of the present invention and / or any related embodiments disclosed above and below.

[0066] It should be understood that according to the first or second aspect of the present invention, one or more embodiments describing the preferred amino acids at the position of Z1 may be combined with one or more embodiments describing the preferred amino acids at the position of Z2 and / or Z3, and vice versa. Therefore, any combination of one or more embodiments mentioned under "preferred amino acids in Z1" may be combined with one or more embodiments mentioned under "preferred amino acids in Z2" and / or "preferred amino acids in Z3", and vice versa. Any such combination of embodiments should be understood as a direct and explicit part of the present invention.

[0067] Referring to the second aspect of the present invention, examples of combinations of the above-mentioned embodiments are:[[]] According to Z1-Z2-Z3 of the second aspect, where Z2 is Z2-Emb4; Z1-Emb1, Z2-Emb2 and Z3-Emb1; Z1-Emb1, Z2-Emb5 and Z3-Emb1; Z1-Emb1, Z2-Emb6 and Z3-Emb1; Z1-Emb2, Z2-Emb2 and Z3-Emb1; Z1-Emb2, Z2-Emb7 and Z3-Emb1; Z1-Emb3, Z2-Emb3 and Z3-Emb2.

[0068] Preferred lipid / linker The polypeptide according to the first and / or second aspect of the present invention may have the general formula L-Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8The structure (i.e., lipid / linker) is at the lysine (K) residue, preferably at amino acid position X 28 is lipidated at the lysine (K) residue in, where L is a lipid selected from 17-carboxy-heptadecanoyl (abbreviated C18DA) and 19-carboxy-nonadecanoyl (abbreviated C20DA), and further where Y 1 -Y 8 each of which is independently selected from: absent, [γE], [E], [OEG], [eLys] or [AHX].

[0069] Preferably, the lipid / linker has the general formula L-Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 The structure of, where L is a lipid selected from C18DA or C20DA, where Y 1 -Y 8 each of which is independently selected from: absent, [γE], [E], [OEG], [eLys] or [AHX], where Y 1 -Y 3 each of which is [γE], or Y 1 -Y 3 each of which is [E], where Y 4 is selected from: [γE], [E] or [OEG], and where Y 5 -Y 8 each of which is independently selected from: absent, [γE], [E], [OEG], [eLys] or [AHX].

[0070] Preferably, the lipid / linker has the general formula L-Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 The structure of, where L is C20DA, where Y 1 -Y 8 each of which is independently selected from: absent, [γE], [E], [OEG] or [eLys], where Y 1 -Y 4 each of which is [γE], or Y 1 -Y 4 each of which is [E], where Y 5Selected from: [γE], [E], [OEG] or [eLys], and wherein Y 6 -Y 8 each of which is independently selected from: absent, [γE], [E], [OEG] or [eLys].

[0071] For example, the polypeptide of the present invention is lipidated at the lysine (K) residue at amino acid position X 28 and the lipid / linker is selected from the group consisting of: C18DA[E][E][E][E]-(SEQ ID NO:640), C18DA[E][E][E][E][E]-(SEQ ID NO:636), C18DA[E][E][E][E][E][E]-(SEQ ID NO:637), C18DA[γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE][γE]-, C18DA[E][E][E][E][E][eLys]-(SEQ ID NO:635), C18DA[E][E][E][E][E][E][eLys]-(SEQ ID NO:643), C18DA[γE][γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][γE][γE][eLys]-, C20DA[E][E][E][E][E][eLys]-(SEQ ID NO:639), C20DA[γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][eLys][eLys]-, C18DA[E][E][E][OEG][OEG]-, C18DA[E][E][E][E][OEG][OEG]-(SEQ IDNO:634), C18DA[γE][γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][γE][γE][OEG][OEG]-, C20DA[E][E][E][E][OEG][OEG]-(SEQ IDNO: 638), C20DA[γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][γE][OEG]-, C18DA[γE][γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][OEG][OEG][eLys]-, C18DA[γE][γE][γE][γE][OEG][OEG][eLys]-, C20DA[γE][γE][γE][OEG][OEG][eLys]-, C20DA[γE][γE][γE][γE][OEG][OEG][eLys]-, C18DA[γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][AHX]-, or C20DA[γE][γE][γE][γE][γE][γE][AHX]-.

[0072] For example, the polypeptide of the present invention is lipidated at the lysine (K) residue at amino acid position X 28 and the lipid / linker is selected from the group consisting of: C20DA[γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE][γE]-, C18DA[E][E][E][E][E][eLys]-(SEQ ID NO:635), C20DA[E][E][E][E][E][eLys]-(SEQ ID NO:639), C20DA[γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][eLys][eLys]-, C20DA[E][E][E][E][OEG][OEG]-(SEQ ID NO:638), C20DA[γE][γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][OEG][OEG][eLys]-.

[0073] The triple agonists of the present invention are generally soluble at about pH 7. Several techniques for measuring solubility are known to those skilled in the art. Preferably, the solubility of the peptides of the present invention is measured as disclosed in Example 2 below.

[0074] In some embodiments, the solubility of the compounds of the present invention is greater than or equal to 1.0 mg / ml at about pH 7.

[0075] In some embodiments, the solubility of the compounds of the present invention is greater than 3.0 mg / ml at about pH 7.

[0076] In some embodiments, the solubility of the compounds of the present invention is greater than 5.0 mg / ml at about pH 7.

[0077] In some embodiments, the solubility of the compounds of the invention is equal to or greater than 6.0 mg / ml, 7.0 mg / ml, 8.0 mg / ml, or 9.0 mg / ml at about pH 7.

[0078] The heteromeric polypeptides of the invention are capable of agonizing hGLP1R, GIPR, and hNPY2R in the presence of human serum albumin (the major protein present in human plasma) (see Table 3). The activity of the peptides of the invention in the presence of human plasma is an important prerequisite for a viable compound for treating the disclosed diseases. Those skilled in the art will appreciate suitable assay formats, and examples are provided below. For example, for the peptides of the invention, in the presence of 100% human plasma (100% hP), the EC 50 values of hGLP1R, GIPR, and hNPY2R are evaluated by the assay described in Example 1 below.

[0079] In some embodiments of the peptides of the invention, the EC 50 for hGLP1R 100% hP and GIPR 100% hP is below 100 nM (e.g., 0.01 nM to 100 nM), and the EC 50 for hNPY2R 100% hP is below 1000 nM (e.g., 0.01 nM to 1000 nM).

[0080] In some embodiments of the peptides of the invention, the EC 50 for hGLP1R 100% hP and GIPR 100% hP is below or equal to 30 nM (e.g., 0.01 nM to 50 nM), and the EC 50 for hNPY2R 100% hP is below 300 nM (e.g., 0.01 nM to 300 nM).

[0081] In some embodiments of the peptides of the invention, the EC 50 for hGLP1R 100% hP and GIPR 100% hP is below or equal to 10 nM (e.g., 0.01 nM to 10 nM), and the EC 50 for hNPY2R 100% hP is below 100 nM (e.g., 0.01 nM to 100 nM).

[0082] In a preferred embodiment of the peptides of the invention, the EC 50 for hGLP1R 100% hP and GIPR 100% hP is below or equal to 10 nM (e.g., 0.01 nM to 10 nM), and the EC 50 for hNPY2R 100% hP is below 100 nM (e.g., 0.01 nM to 100 nM), and the solubility is greater than or equal to 1.0 mg / ml at about pH 7.

[0083] In some embodiments, the peptides of the invention have advantageous pharmacokinetic properties. In this regard, the in vivo half-life of the peptides of the invention in mice (NMRI mice, see the measurements described in Example 3) can be greater than 6 hours or greater than 8 hours or greater than 10 hours.

[0084] In a preferred embodiment of the peptides of the invention, the EC 50 for hGLP1R 100% hP and GIPR 100% hP is less than or equal to 10 nM (e.g., 0.01 nM to 10 nM), and the EC 50 for hNPY2R 100% hP is less than 100 nM (e.g., 0.01 nM to 100 nM), the solubility is greater than or equal to 1.0 mg / ml at about pH 7, and the in vivo half-life is greater than 8 hours.

[0085] In a third aspect, the present invention provides a polypeptide for use as a medicament. Since the Y2 receptor has an appetite-suppressing effect, polypeptides having Y2 agonist activity are applicable to the treatment of symptoms related to eating disorders, obesity (e.g., simple obesity or symptomatic obesity), and / or diabetes. In addition, the gut hormones GLP-1 and GIP (referred to as incretins) promote pancreatic insulin secretion. Since incretins are closely related to glucose metabolism, polypeptides having GLP-1 receptor agonist activity and GIP receptor agonist activity are applicable to the treatment of symptoms related to glucose metabolism disorders (including diabetes and obesity). Therefore, the polypeptides of the present invention may have an appetite-suppressing effect and / or a weight loss effect. In a preferred embodiment, the present invention provides a polypeptide for preventing, treating, and / or ameliorating a disease, disorder, or condition selected from the list consisting of: overweight (obesity), obesity (e.g., simple obesity (long-term weight management) or symptomatic obesity), insulin resistance, diabetes (e.g., type 1 diabetes or type 2 diabetes) or prediabetes, eating disorders, hyperlipidemia (e.g., hypertriglyceridemia, hypercholesterolemia, high LDL-cholesterolemia, low HDL-cholesterolemia, postprandial hyperlipidemia), metabolic syndrome (three of the following five medical conditions: abdominal obesity, hypertension, hyperglycemia, high serum triglycerides, and low serum high-density lipoprotein (HDL)), liver diseases, such as metabolic associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), portal hypertension; cardiovascular diseases (e.g., hypertension, atherosclerosis, stroke, or heart failure); kidney diseases, such as diabetic kidney disease (DKD) and chronic kidney disease (CKD); and neurodegenerative diseases (Alzheimer's disease or Parkinson's disease), as well as other obesity-related diseases, such as osteoporosis, sleep apnea, obesity-related cancer, and obesity-related asthma. Examples of symptomatic obesity include endocrine obesity (e.g., Cushing syndrome, hypothyroidism, insulinoma, obesity type 2 diabetes, pseudohypoparathyroidism, hypogonadism, and related endocrine disorders, such as polycystic ovary syndrome (PCOS)), central obesity (e.g., hypothalamic obesity, frontal lobe syndrome, Kleine-Levin syndrome), genetic obesity (e.g., Prader-Willi syndrome, Laurence-Moon-Biedl syndrome), drug-induced obesity (e.g., steroid, phenothiazine, insulin, sulfonylurea agent, β-blocker-induced obesity).

[0086] The polypeptides of the present invention can also be used to prevent obesity, or to prevent or reverse obesity and / or the comorbidities of overweight, such as type 2 diabetes, hypertension, NAFLD, NASH, DKD, CKD, sleep apnea, obesity-related cancers or obesity-related asthma.

[0087] In a fourth aspect, the present invention provides a method for treating a disease, disorder and / or condition, the method comprising administering to an individual in need thereof a therapeutically effective amount of a polypeptide or a pharmaceutically acceptable salt thereof according to any one of the aspects and embodiments disclosed herein. Preferably, the disease, disorder and / or condition is selected from the list consisting of: overweight, obesity, diabetes (type 1 or type 2) or prediabetes, eating disorders, hyperlipidemia, metabolic syndrome, NAFLD, NASH and / or cardiovascular diseases. Most preferably, the disease, disorder and / or condition is obesity, prediabetes and / or diabetes (type 1 or type 2).

[0088] Furthermore, the present invention provides a method of binding and / or activating GLP-1, GIP and hNPY2 receptors in an individual in need thereof, the method comprising administering a therapeutically effective amount of a polypeptide or a pharmaceutically acceptable salt thereof according to any one of the aspects and embodiments disclosed herein.

[0089] Similarly, the present invention relates to the use of a polypeptide or a pharmaceutically acceptable salt thereof according to any one of the aspects and embodiments disclosed herein for the manufacture of a medicament for treating a disease, disorder and / or condition.

[0090] For humans (subcutaneous administration), the weekly applicable dose range of the polypeptide of the general structure according to formula (I) is usually 0.01 to 100 mg.

[0091] The polypeptides of the present invention can be administered subcutaneously using a suitable device, such as a pre-filled ready-to-use injection device, syringe, pen injector or autoinjector.

[0092] The actual pharmaceutically effective amount or therapeutic dose will generally depend on factors known to those skilled in the art, such as the age and weight of the patient, the route of administration and the severity of the disease. In any case, the compound will be administered in a dose and manner that allows for the delivery of a pharmaceutically effective amount based on the patient's unique condition. Examples

[0094] General procedure for solid-phase synthesis of peptides All peptides were synthesized on Tentagel S RAM resin (loading 0.23 to 0.25 mmol / g, bead size 90 μm) supplied by Iris Biotech GmbH or RappPolymere GmbH by standard Fmoc-based solid-phase peptide chemistry methods.

[0095] The following protected amino acids are used: Fmoc-Ala-OH, Fmoc-Aib-OH, Fmoc-Arg(Pbf)-OH, Fmoc-NMeArg(Pbf)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Asp(tBu)-OH, Fmoc-Gln(Trt)-OH, Fmoc-NMeGln(Trt)-OH, Fmoc-Glu(tBu)-OH, Fmoc-Glu-OtBu, Fmoc-Gly-OH, Fmoc-His(Trt)-OH, Fmoc-Ile-OH, Fmoc-Leu-OH, Fmoc-Lys(Boc)-OH, Fmoc-Lys(Dde)-OH, Fmoc-Lys(Mtt)-OH, Fmoc-Phe-OH, Fmoc-Pro-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Trp(Boc)-OH, Fmoc-Tyr(tBu)-OH, Boc-Tyr(tBu)-OH, Fmoc-D-Tyr(tBu)-OH, Fmoc-Val-OH. Unless otherwise specified, amino acid building blocks in the L-form are utilized.

[0096] Modular half-life extension groups are established using protected building blocks via solid-phase peptide synthesis (SPPS), said building blocks being, for example (but not limited to), C18DA(tBu), C20DA(tBu), Fmoc-OEG-OEG-OH, Fmoc-OEG-OH, Boc-Lys(Fmoc)-OH, Fmoc-Glu-OtBu, Fmoc-Glu(tBu)-OH, Fmoc-Ahx-OH, Fmoc-Trx-OH and Fmoc-Sar-OH.

[0097] Amino acids, Fmoc-Glu-OtBu, Oxyma and DIC were purchased from standard suppliers such as Bachem, Novabiochem, ABCR GmbH&CO.KG., Iris Biotech GmbH, Sigma-Aldrich. C18DA(tBu) and C20DA(tBu) were supplied by Cool Pharm Ltd. or AstraTech, Fmoc-OEG-OEG-OH was supplied by ABCR GmbH&CO.KG or Iris Biotech GmbH, and Fmoc-OEG-OH was supplied by Angene International Limited, Combi Blocks Inc., Iris Biotech GmbH or Hangzhou APIChem Technology Co., Ltd. Fmoc-Ahx-OH was purchased from Activate Scientific GmbH, and Fmoc-Trx-OH was purchased from ABCR GmbH&CO.KG.

[0098] Peptide assembly starts from the C-terminus and the chain is gradually extended towards the N-terminus according to the individual sequence until the N-terminal amino acid is reached. After deprotection of the side chain of the branched amino acid (such as Lys(Dde)), the assembly of the half-life extension group follows.

[0099] The peptide was obtained in the form of TFA salt by cleavage / deprotection or purified by HPLC. The trifluoroacetate salt can be exchanged by common procedures such as resin ion exchange procedures, as disclosed, for example, by Roux, St. et al., J. Pept. Sci. 2008; 14: 354-359.

[0100] Synthesis method 1 (S01) The peptide was synthesized by microwave-assisted solid-phase peptide synthesis (SPPS) using the Fmoc strategy on Tentagel S RAM resin at a scale of 0.25 mmol on a CEM Liberty Blue peptide synthesizer. The stoichiometry and concentration of the peptide coupling reaction were 4 equivalents of DMF (0.2 mol / l, 5 ml) containing the appropriately protected amino acid, 4 equivalents of DMF (1 mol / l, 1 ml) containing Oxyma, and 8 equivalents of DMF (1 mol / l, 2 ml) containing DIC.

[0101] The reaction times and temperatures of the amino acids vary. A single coupling for 4 minutes at 90 °C is applicable to all standard amino acids except for the following amino acids. A single coupling for 20 minutes at 75 °C is applicable to Fmoc-Aib-OH, and the amino acids following Aib are coupled twice. A double coupling for 4 minutes at 90 °C is applicable to Fmoc-Arg(Pbf)-OH, C18DA(tBu), C20DA(tBu), Fmoc-OEG-OH, Fmoc-NMeArg(Pbf)-OH, and Fmoc-NMeGln(Trt)-OH. The amino acids following NMeArg and NMeGln are coupled twice. The last 8 standard amino acids in the main chain are coupled for 8 minutes at 90 °C.

[0102] Before and after the coupling of Fmoc-Glu-OtBu and before the coupling of C18DA(tBu) and C20DA(tBu), a capping step is carried out for 5 minutes at 65 °C with DMF (10 ml) containing 20% acetic anhydride. The N α Fmoc deprotection is carried out for 1 minute. The deprotection of the Lys(Dde)-group is carried out twice for 3 minutes at 90 °C with DMF (10 ml) containing 5% hydrazine hydrate. The crude product is washed on the resin with DCM and dried before cleavage. Cleavage from the resin and deprotection are carried out for 45 minutes at 40 °C with a mixture of 95% TFA / water (10 ml) and triisopropylsilane (250 μl). The crude peptide is precipitated with cold tert-butyl methyl ether, dissolved in 50% acetonitrile / water, and purified by preparative HPLC.

[0103] Synthesis method 2 (S02) Peptides were synthesized by SPPS on a MultiSynTech SYRO II on a 0.2 mmol scale. Standard coupling of amino acids was achieved by using 4 equivalents of the appropriately protected amino acids (0.5 mol / l) dissolved in 0.5 mol / l Oxyma-DMF solution and 4.5 equivalents of DIC (1 mol / l) in DMF. Fmoc-Phe-OH was dissolved in 0.5 mol / l Oxyma-NMP and 4 equivalents were used for coupling (0.5 mol / l). The coupling time for the first 23 amino acids from the C-terminus was 15 minutes at 75 °C (Cys and His were coupled at 50 °C). Further elongation was carried out by double coupling (2×15 minutes at 75 °C). Selective deprotection of the Lys(Mtt)-group was carried out using hexafluoroisopropanol (10×10 minutes, 10 ml at room temperature). Derivatization of the deprotected lysine intermediate was carried out by double coupling of 4 equivalents of the relevant linker building blocks (Fmoc-OEG-OEG-OH, Fmoc-Glu-OtBu, Boc-Lys(Fmoc)-OH, C18DA(tBu), C20DA(tBu)) for 15 minutes at 75 °C. N α Fmoc deprotection was carried out using NMP (4 ml) containing 40% piperidine for 3 minutes, followed by NMP (4 ml) containing 20% piperidine for 15 minutes at 45 °C. The appropriately protected Fmoc-Asp, Fmoc-Cys and Fmoc-His intermediates were deprotected at room temperature. The peptide was cleaved from the resin and side chains were deprotected by adding 15 ml of 95:2:1:2 TFA / DODT / TES / water at room temperature for 4 hours or at 45 °C for 60 minutes. The peptide was precipitated with cold diethyl ether, dissolved in acetonitrile / water and purified by preparative HPLC (Purification method 3, P02).

[0104] Purification method 1 (P01) The crude peptide was dissolved in DMF / acetonitrile / water and purified by reverse phase chromatography using an Agilent preparative HPLC-MS system with preparative pumps G7161B, G7111B and G7110B, diode array detector G7115A, mass spectrometer G6135B and fraction collector G7158B. A Waters Luna preparative C8(3) column ( 10 μm, 300 g, self-packed steel column) served as the stationary phase. The mobile phase was run at a flow rate of 150 ml / min at 40 °C with a gradient of buffer A (ACN) and buffer (H2O + 0.1% TFA) as described in the table below. The relevant fractions were combined and lyophilized. The final product was characterized by analytical HPLC-MS (U046_001 and U046_006).

[0105] Purification method 2 (P02) The crude peptide was dissolved in DMF / acetonitrile / water and purified by reverse-phase chromatography using a GILSON preparative HPLC system, which consisted of a preparative pump AP-MOD (maximum flow rate: 200 mL / min), a diode array detector ECOMFlash 10, and a fraction collector GILSON GX 281. The stationary phase was a Phenomenex LUNAC8 10 μm preparative column (50×250 mm). The peptide was eluted with a focusing gradient using water (eluent A) and acetonitrile (eluent B) at a flow rate of 120 mL / min and 40 °C; a modifier solution was added in the "column dilution mode" to maintain a constant amount of 0.1% TFA in the mobile phase. The homogeneous fractions were combined and lyophilized. The final product was characterized by HPLC-MS (U046_001 and U046_006).

[0106] Purification method 3 (P03) The crude peptide was purified by reverse-phase HPLC using a Waters preparative HPLC system, which consisted of a C8 column (Reprosil Gold 5 μm, 40 mm×250 mm), a preparative pump (Waters2545), a UV / VIS detector (Waters 2489), and a Waters fraction collector III. The mobile phase was run with a gradient of buffer A (H2O containing 0.1% TFA) and buffer B (ACN containing 0.1% TFA, gradient: 35 to 45% in 20 minutes) at a flow rate of 50 mL / min at room temperature. The relevant fractions were analyzed, combined, and lyophilized. The final product was characterized by analytical UPLC-MS (A02).

[0107] Analytical method 1 (A01-A / B) The peptide purity and mass were estimated by analytical HPLC-MS on a Kinetex C8 column (4.6 mm×150 mm, 2.6 μm, Phenomenex) using an Agilent 1260 HPLC system equipped with a mass detector G6135. The analysis was performed by gradient elution with buffer A (H2O containing 0.3% TFA) and buffer B (ACN containing 0.24% TFA) at a temperature of 40 °C. The details of the gradient and flow rate are summarized in the table below. The retention time and mass were recorded.

[0108] The peptide purity (relative peak area at 214 nm) was in the range of 80 to 99%, preferably greater than 95%.

[0109] Analysis method 2 (A02 - A / B) The peptide purity and mass were determined by analytical HPLC - MS on a Kinetex C8 column (Phenomenex, 2.6 μm, 4.6 mm × 150 mm) using a Waters Acquity HPLC system equipped with a 3100 mass detector. The analysis was carried out by gradient elution with buffer A (H2O containing 0.3% TFA) and buffer B (ACN containing 0.3% TFA) at a temperature of 40 °C. Details of the gradient and flow rate are outlined in the table below. The retention time and mass were recorded.

[0110] List of abbreviations ACN: Acetonitrile AHX: 6 - Aminohexanoic acid Aib: Amino - isobutyric acid aMeF: α - Methyl - L - phenylalanine bh - Gln: β - homo - L - glutamine Boc: tert - Butyloxycarbonyl Chg: Cyclohexyl - glycine C18DA(tBu): 18 - (tert - butoxy) - 18 - oxooctadecanoic acid C20DA(tBu): 20 - (tert - butoxy) - 20 - oxoeicosanoic acid D - Arg: D - Arginine D - Asp: D - Aspartic acid DCM: Dichloromethane DIC: Diisopropylcarbodiimide DIPEA: Diisopropylethylamine Dde: (4,4 - Dimethyl - 2,6 - dioxocyclohex - 1 - ylidene)ethyl D - His: D - Histidine D - Leu: D - Leucine DMF: N,N - Dimethylformamide DODT: 3,6 - Dioxaoctane - 1,8 - dithiol DPBS: Dulbecco's phosphate - buffered saline D - Tyr: D - Tyrosine eLys: N-ε-L-lysine Fmoc: 9H-fluoren-9-ylmethoxycarbonyl Fmoc-Ahx: 6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoic acid Fmoc-OEG-OH: 2-[2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]acetic acid Fmoc-OEG-OEG-OH: 2-[2-[2-[[2-[2-[2-(9H-fluoren-9-ylmethoxycarbonyl-amino)ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetic acid gGlu: C-γ-L-glutamic acid hArg: homo-L-arginine HTRF: homogeneous time-resolved fluorescence IBMX: 3-isobutyl-1-methylxanthine Iva: 2-amino-2-methylbutyric acid iVal: 3-methylbutanoyl (isovaleryl) MRT: mean retention time Mtt: 4-methyl-triphenylmethyl NMeR: N-methyl-L-arginine NMeQ: N-methyl-L-glutamine NMeY: N-methyl-L-tyrosine NMP: 1-methyl-pyrrolidin-2-one Oxyma: ethyl 2-cyano-2-(hydroxyimino)acetate OEG: 2-[2-(2-aminoethoxy)ethoxy]acetic acid Phg: S-phenylglycine Pbf: 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl Rt: retention time RT: room temperature Sarcosine: N-methyl-glycine SPPS: solid-phase peptide synthesis tBu: tert-butyl Tle: L-tert-butylglycine Trt: triphenylmethyl TRX: Tranexamic acid, trans-4-(aminomethyl)cyclohexane-1-carboxylic acid TES: triethylsilane TFA: trifluoroacetic acid

[0111] Synthesize the following compounds. All compounds are obtained as TFA salts:

[0112] Compound 2 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-I-E-L-R-H-F-L-N-H-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:328) MW (Calculated): 6869.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.8 minutes; m / 3: m / 4: 1718.1 m / 5:

[0113] Compound 3 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-Q-R-S-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:329) MW (Calculated): 7106.0 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.7 minutes; m / 3: 2370.2 m / 4: 1777.9 m / 5:

[0114] Compound 4 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-Aib-R-H-Y-Aib-N-R-Aib-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:330) MW (Calculated): 6736.5 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.0 minutes; m / 3: m / 4: 1684.9 m / 5:

[0115] Compound 5 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-DLeu-R-DHis-Y-Y-N-W-L-T-DArg-Q-R-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:331) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.8 minutes; m / 3: m / 4: 1726.0 m / 5:

[0116] Compound 6 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-Q-R-Y-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:332) MW (Calculated): 7182.1 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 8.0 minutes; m / 3: 2395.5 m / 4: 1797.0 m / 5:

[0117] Compound 7 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-E-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys-eLys(1,2) (SEQ ID NO:333) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.9 minutes; m / 3: m / 4: 1725.9 m / 5:

[0118] Compound 8 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-Q-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:334) MW (Calculated): 6957.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.5 minutes; m / z: 2320.3 m / z: 1740.7 m / z:

[0119] Compound 9 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-Y-V-S-I-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:335) MW (Calculated): 7034.9 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.7 minutes; m / z: 2346.7 m / z: 1760.1 m / z:

[0120] Compound 10 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-E-S-Aib-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eK (SEQ ID NO:336) MW (Calculated): 6970.8 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.1 minutes; m / z: 2324.9 m / z: 1743.9 m / z:

[0121] Compound 11 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:337) MW (Calculated): 6724.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.8 minutes; m / 3: 2242.2 m / 4: 1681.8 m / 5:

[0122] Compound 12 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:338) MW (Calculated): 6696.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / 3: 2232.7 m / 4: 1674.9 m / 5:

[0123] Compound 13 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-Aib-R-H-Y-Y-N-R-Aib-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:339) MW (Calculated): 6814.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 33.6 minutes; m / 3: m / 4: 1704.5 m / 5:

[0124] Compound 14 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-R-Y-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:340) MW (Calculated): 7151.1 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / 3: 2385.6 m / 4: 1789.2 m / 5:

[0125] Compound 15 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-Y-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:341) MW (Calculated): 7033.9 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.6 minutes; m / 3: 2346.2 m / 4: 1759.9 m / 5:

[0126] Compound 16 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-Aib-E-A-Q-Aib-K-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:342) MW (Calculated): 6915.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 38.2 minutes; m / 3: m / 4: 1729.7 m / 5:

[0127] Compound 17 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-L-N-L-Aib-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:343) MW (Calculated): 6749.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.1 minutes; m / 3:m / 4:1688.1 m / 5:

[0128] Compound 18 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Aib-N-R-Aib-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:344) MW (Calculated): 6764.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.3 minutes; m / 3:m / 4:1691.9 m / 5:

[0129] Compound 19 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-Y-Y-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:345) MW (Calculated): 7110.0 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.6 minutes; m / 3:2370.9 m / 4:1778.2 m / 5:

[0130] Compound 20 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-A-A-A-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:346) MW (Calculated): 6728.5 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 39.8 minutes; m / 3: m / 4: 1682.9 m / 5:

[0131] Compound 21 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-DHis-Y-Y-N-W-L-T-DArg-Q-R-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:347) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.0 minutes; m / 3: m / 4: 1725.9 m / 5:

[0132] Compound 22 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-Q-S-S-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:348) MW (Calculated): 7036.9 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / 3: 2347.4 m / 4: 1760.7 m / 5:

[0133] Compound 23 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-Y-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:349) MW (Calculated): 6994.9 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.4 minutes; m / z: 2331.8 m / z: 1749.4 m / z:

[0134] Compound 24 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-Aib-K-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:350) MW (Calculated): 6915.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.6 minutes; m / z: m / z: 1723.2 m / z:

[0135] Compound 25 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-A-A-K-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:351) MW (Calculated): 6843.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 37.2 minutes; m / z: m / z: 1711.7 m / z:

[0136] Compound 26 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-Aib-R-H-Y-Y-N-W-L-T-hArg-Q-R-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:352) MW (Calculated): 6886.7 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 34.3 minutes; m / 3: m / 4: 1722.4 m / 5:

[0137] Compound 27 Structure disclosed SEQ ID NO:353 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-V-S-I-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:353) MW (Calculated): 6928.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / 3: 2311.6 m / 4: 1733.8 m / 5:

[0138] Compound 28 Structure disclosed SEQ ID NO:354 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:354) MW (Calculated): 6829.6 Da Synthesis and purification method: S01; P02 LCMS: A01 - A; Rt: 13.3 minutes; m / z:m / 4:1708.0m / 5:

[0139] Compound 29 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu(1,2) (SEQ ID NO:355) MW (calculated): 6684.5 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.7 minutes; m / z:2228.8m / 4:1672.0m / 5:

[0140] Compound 30 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - E - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:356) MW (calculated): 6900.7 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 36.2 minutes; m / z:m / 4:1725.9m / 5:

[0141] Compound 31 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - E - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - Q - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:357) MW (calculated): 6958.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.6 minutes; m / z: 2320.8 m / z: 1740.7 m / z:

[0142] Compound 32 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:358) MW (calculated): 6974.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.7 minutes; m / z: 2325.7 m / z: 1744.4 m / z:

[0143] Compound 33 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - A - V - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:359) MW (calculated): 6942.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.5 minutes; m / z: 2316.3 m / z: 1737.1 m / z:

[0144] Compound 34 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - E - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:360) MW (calculated): 6771.6 Da Synthesis and purification method: S01; P01 LCMS: A01 - B; Rt: 36.4 minutes; m / z:m / 4:1693.6 m / 5:

[0145] Compound 35 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - S - G - E - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eK(SEQ ID NO:361) MW (calculated): 6957.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 6.2 minutes; m / z:2320.5 m / 4:1740.4 m / 5:

[0146] Compound 36 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - E - F - V - Q - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2)(SEQ ID NO:362) MW (calculated): 6990.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.6 minutes; m / z:2331.2 m / 4:1748.3 m / 5:

[0147] Compound 37 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2)(SEQ ID NO:363) MW (calculated): 6941.8 Da Synthesis and purification method: S01; L20 LCMS: A01 - A; Rt: 7.2 minutes; m / z: 2314.9 m / z: 1736.3 m / z:

[0148] Compound 38 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - V - S - Aib - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:364) MW (calculated): 6900.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 6.1 minutes; m / z: 2301.4 m / z: 1726.2 m / z:

[0149] Compound 39 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - Aib - R - H - Y - Y - N - W - L - T - R - Q - NMeR - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:365) MW (calculated): 6886.7 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 34.4 minutes; m / z: m / z: 1722.3 m / z:

[0150] Compound 40 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - Y - V - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:366) MW (calculated): 7034.9 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.5 minutes; m / z: 2345.5 m / z: 1759.4 m / z:

[0151] Compound 41 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - P - Q - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:367) MW (calculated): 6997.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 10.4 minutes; m / z: 2333.6 m / z: 1750.6 m / z:

[0152] Compound 42 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - E - Y - V - S - I - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:368) MW (calculated): 7076.9 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.7 minutes; m / z: 2360.0 m / z: 1770.6 m / z:

[0153] Compound 43 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - E - F - V - Q - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:369) MW (calculated): 7086.9 Da Synthesis and purification method: S01; P02 LCMS: A01 - A; Rt: 12.3 minutes; m / z: m / 4: 1772.6 m / 5:

[0154] Compound 44 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - Q - S - Aib - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:370) MW (calculated): 6929.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 6.0 minutes; m / z: 2311.2 m / 4: 1733.2 m / 5:

[0155] Compound 45 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - E - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - OEG - eLys(1,2) (SEQ ID NO:371) MW (calculated): 6916.7 Da Synthesis and purification method: S01; P01 LCMS: A01 - B; Rt: 36.2 minutes; m / z: m / 4: 1729.8 m / 5:

[0156] Compound 46 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - E - A - Q - Aib - K - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:372) MW (calculated): 6958.8 Da Synthesis and purification method: S01; P02 LCMS: A01-B; Rt: 34.6 minutes; m / z:m / 4: 1740.5 m / 5:

[0157] Compound 47 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:373) MW (calculated): 6927.8 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.7 minutes; m / z: 2310.9 m / 4: 1733.2 m / 5:

[0158] Compound 48 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-P-Q-S-I-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:374) MW (calculated): 7039.9 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.1 minutes; m / z: 2347.9 m / 4: 1761.1 m / 5:

[0159] Compound 49 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-E-S-Aib-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:375) MW (calculated): 6930.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 6.1 minutes; m / z: 2311.3 m / z: 1733.7 m / z:

[0160] Compound 50 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - Y - E - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:376) MW (calculated): 7064.9 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.4 minutes; m / z: 2356.2 m / z: 1767.5 m / z:

[0161] Compound 51 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - E - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:377) MW (calculated): 6872.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 5.7 minutes; m / z: 2291.8 m / z: 1719.6 m / z:

[0162] Compound 52 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - E - E - E - E - OEG - OEG(1,2) (SEQ ID NO:378) MW (calculated): 6817.6 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 10.3 minutes; m / z: 2273.8 m / z: 1705.5 m / z:

[0163] Compound 53 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu(1,2)(SEQ ID NO:379) MW (calculated): 6656.4 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.9 minutes; m / z: 2219.5 m / z: 1664.9 m / z:

[0164] Compound 54 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - E - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - eLys(1,2)(SEQ ID NO:380) MW (calculated): 6696.5 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 5.9 minutes; m / z: 2232.8 m / z: 1675.3 m / z:

[0165] Compound 55 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2)(SEQ ID NO:381) MW (calculated): 6946.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.1 minutes; m / z: 2316.4 m / z: 1737.6 m / z:

[0166] Compound 56 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - E - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:382) MW (calculated): 6874.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.2 minutes; m / z: 2292.4 m / z: 1719.8 m / z:

[0167] Compound 57 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - E - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:383) MW (calculated): 6899.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.1 minutes; m / z: 2300.8 m / z: 1725.9 m / z:

[0168] Compound 58 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:384) MW (calculated): 6817.6 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 10.0 minutes; m / z: 2273.4 m / z: 1705.5 m / z:

[0169] Compound 59 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - Y - Y - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:385) MW (calculated): 6952.9 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: minutes; m / z: 2318.5 m / z: 1738.9 m / z:

[0170] Compound 60 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:386) MW (calculated): 6784.6 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 9.2 minutes; m / z: 2262.5 m / z: 1697.3 m / z:

[0171] Compound 61 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:387) MW (calculated): 6812.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.4 minutes; m / z: 2271.8 m / z: 1704.2 m / z:

[0172] Compound 62 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - R - Y - Y - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2)(SEQ ID NO:388) MW (calculated): 7152.1 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 35.2 minutes; m / z: m / z: 1788.8 m / z:

[0173] Compound 63 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - E - E - E - E - E - eLys(1,2)(SEQ ID NO 389 and 635 respectively) MW (calculated): 6784.6 Da Synthesis and purification methods: S02; P03 LCMS: A02 - B; Rt: 9.6 minutes; m / z: 2262.4 m / z: 1697.1 m / z:

[0174] Compound 64 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - E - S - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2)(SEQ ID NO:390) MW (calculated): 6858.7 Da Synthesis and purification methods: S02; P03 LCMS: A02 - A; Rt: 7.1 minutes; m / z: 2286.9 m / z: 1715.2 m / z:

[0175] Compound 65 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - G - S - E - Y - V - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu(1,2) (SEQ ID NO:391) MW (calculated): 6908.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.4 minutes; m / z: 2345.9 m / z: 1760.1 m / z:

[0176] Compound 66 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - E - E - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:392) MW (calculated): 6902.7 Da Synthesis and purification method: S01; P02 LCMS: A01 - A; Rt: 14.1 minutes; m / z: m / z: 1726.5 m / z:

[0177] Compound 67 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - E - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:393) MW (calculated): 6894.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.1 minutes; m / z: 2298.9 m / z: 1724.2 m / z:

[0178] Compound 68 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - R - Aib - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:394) MW (calculated): 6842.7 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 34.3 minutes; m / z: m / z: 1711.4 m / z:

[0179] Compound 69 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - E - K - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:395) MW (calculated): 6958.8 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 33.8 minutes; m / z: m / z: 1740.4 m / z:

[0180] Compound 70 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - E - S - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:396) MW (calculated): 6853.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.3 minutes; m / z: 2284.9 m / z: 1714.4 m / z:

[0181] Compound 71 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - hArg - Q - R - D Tyr - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:397) MW (calculated): 6914.8 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 34.7 minutes; m / z: m / z: 1729.4 m / z:

[0182] Compound 72 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - D - L - R - H - Y - L - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:398) MW (calculated): 6878.7 Da Synthesis and purification method: S01; P01 LCMS: A01 - B; Rt: 36.2 minutes; m / z: m / z: 1720.4 m / z:

[0183] Compound 73 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - P - E - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:399) MW (calculated): 6998.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 6.3 minutes; m / z: 2334.1 m / z: 1751.0 m / z:

[0184] Compound 74 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - Aib - R - H - Y - Y - N - W - L - T - R - Q - R - DTyr - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:400) MW (calculated): 6872.7 Da Synthesis and purification method: S01; P01 LCMS: A01 - B; Rt: 34.3 minutes; m / z: m / z: 1718.8 m / z:

[0185] Compound 75 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - Y - Y - V - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:401) MW (calculated): 6981.9 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.6 minutes; m / z: 2328.1 m / z: 1746.1 m / z:

[0186] Compound 76 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - Aib - R - H - Y - Aib - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:402) MW (calculated): 6794.6 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 34.9 minutes; m / z:m / 4:1699.4m / 5:

[0187] Compound 77 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - E - E - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2)(SEQ ID NO:403) MW(calculated): 6927.8 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.8 minutes; m / z:2310.2m / 4:1733.1m / 5:

[0188] Compound 78 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - Y - V - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2)(SEQ ID NO:404) MW(calculated): 7076.0 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.4 minutes; m / z:2358.9m / 4:1769.7m / 5:

[0189] Compound 79 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - L - Aib - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2)(SEQ ID NO:405) MW(calculated): 6799.6 Da Synthesis and purification method: S01; P02 LCMS: A01-B; Rt: 34.9 minutes; m / z: m / 4: 1700.6 m / 5:

[0190] Compound 80 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-Y-Y-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:406) MW (calculated): 7111.0 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.7 minutes; m / z: 2370.9 m / 4: 1778.5 m / 5:

[0191] Compound 81 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-E-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:407) MW (calculated): 6747.5 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.1 minutes; m / z: 2250.8 m / 4: 1688.3 m / 5:

[0192] Compound 82 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:408) MW (calculated): 6886.7 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 11.4 minutes; m / z: 2296.2 m / z: 1722.4 m / z:

[0193] Compound 83 Structure disclosed as SEQ ID NO:409 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-NMeR-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:409) MW (calculated): 6914.8 Da Synthesis and purification method: S01; P02 LCMS: A01-B; Rt: 35.0 minutes; m / z: m / z: 1729.4 m / z:

[0194] Compound 84 Structure disclosed as SEQ ID NO:410 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-Q-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:410) MW (calculated): 6957.8 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / z: 2320.5 m / z: 1740.5 m / z:

[0195] Compound 85 Structure disclosed as SEQ ID NO:411 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-NMeQ-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:411) MW (Calculated): 6914.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.7 minutes; m / 3:m / 4:m / 5: 1383.8

[0196] Compound 86 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-L-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:412) MW (Calculated): 6850.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.9 minutes; m / 3:m / 4: 1713.5 m / 5:

[0197] Compound 87 Y-Aib-D-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:413) MW (Calculated): 6886.7 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 35.4 minutes; m / 3:m / 4: 1722.4 m / 5:

[0198] Compound 88 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:414) MW (Calculated): 7087.9 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.4 minutes; m / 3: m / 4: 1772.7 m / 5:

[0199] Compound 89 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:415) MW (Calculated): 6983.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.6 minutes; m / 3: 2328.9 m / 4: 1746.9 m / 5:

[0200] Compound 90 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-D-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:416) MW (Calculated): 6887.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.3 minutes; m / 3: m / 4: 1722.7 m / 5:

[0201] Compound 91 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-T-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:417) MW (Calculated): 6914.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.4 minutes; m / 3: 2306.6 m / 4: 1730.1 m / 5:

[0202] Compound 92 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:418) MW (Calculated): 7028.9 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / 3: 2343.6 m / 4: 1758.1 m / 5:

[0203] Compound 93 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-Y-E-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:419) MW (Calculated): 7106.9 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.8 minutes; m / 3: 2370.5 m / 4: 1777.8 m / 5:

[0204] Compound 94 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-I-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:420) MW (Calculated): 6942.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 11.1 minutes; m / 3: 2315.9 m / 4: 1737.1 m / 5:

[0205] Compound 95 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:421) MW (Calculated): 6940.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.8 minutes; m / 3: m / 4: 1735.9 m / 5:

[0206] Compound 96 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:422) MW (Calculated): 6928.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / 3: 2310.1 m / 4: 1732.7 m / 5:

[0207] Compound 97 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:423) MW (Calculated): 6643.4 Da Synthesis and purification methods: S01; P01 LCMS: A01 - B; Rt: 36.9 minutes; m / 3: m / 4: 1661.5 m / 5:

[0208] Compound 98 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-A-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:424) MW (Calculated): 6914.8 Da Synthesis and purification methods: S02; P03 LCMS: A02 - B; Rt: 11.0 minutes; m / 3: 2306.3 m / 4: 1730.1 m / 5:

[0209] Compound 99 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-G-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:425) MW (Calculated): 6829.6 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 36.8 minutes; m / 3: m / 4: 1708.1 m / 5:

[0210] Compound 100 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG-eLys(1,2) (SEQ ID NO:426) MW (Calculated): 6933.8 Da Synthesis and purification methods: S01; P01 LCMS: A01 - B; Rt: 36.5 minutes; m / 3: m / 4: 1734.0 m / 5:

[0211] Compound 101 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:427) MW (Calculated): 6981.8 Da Synthesis and purification methods: S01; L20 LCMS: A01 - B; Rt: 7.4 minutes; m / 3: 2328.2 m / 4: 1746.3 m / 5:

[0212] Compound 102 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-A-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:428) MW (Calculated): 6843.6 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 37.5 minutes; m / 3: m / 4: m / 5: 1369.4

[0213] Compound 103 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-Tle-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:429) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 34.9 minutes; m / 3:m / 4:m / 5: 1380.9

[0214] Compound 104 Y-Aib-E-G-T-F-T-S-D-Y-S-I-L-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:430) MW (Calculated): 6928.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.4 minutes; m / 3:m / 4: 1732.9 m / 5:

[0215] Compound 105 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys-eLys(1,2) (SEQ ID NO:431) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.9 minutes; m / 3:m / 4: 1725.9 m / 5:

[0216] Compound 106 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-I-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:432) MW (Calculated): 6850.7 Da Synthesis and purification method: S01; P01 LCMS: A01-B; Rt: 35.9 minutes; m / 3:m / 4:m / 5: 1370.8

[0217] Compound 107 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-L-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:433) MW (Calculated): 6942.8 Da Synthesis and purification method: S01; P02 LCMS: A01-B; Rt: 35.7 minutes; m / 3:m / 4: 1736.4 m / 5:

[0218] Compound 108 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:434) MW (Calculated): 6854.7 Da Synthesis and purification method: S01; P02 LCMS: A01-A; Rt: 12.9 minutes; m / 3:m / 4: 1714.4 m / 5:

[0219] Compound 109 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-L-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:435) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 35.2 minutes; m / 3: m / 4: 1725.9 m / 5:

[0220] Compound 110 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-eLys(1,2) (SEQ ID NO:436) MW (Calculated): 6917.7 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 36.5 minutes; m / 3: m / 4: 1730.1 m / 5:

[0221] Compound 111 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:437) MW (Calculated): 7014.9 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 9.8 minutes; m / 3: 2339.5 m / 4: 1754.9 m / 5:

[0222] Compound 112 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:438) MW (Calculated): 6932.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.8 minutes; m / z: 2312.2 m / z: 1734.1 m / z:

[0223] Compound 113 Y-Aib-E-G-T-F-T-S-D-L-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:439) MW (Calculated): 6891.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.7 minutes; m / z: m / z: 1723.7 m / z:

[0224] Compound 114 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:440) MW (Calculated): 6969.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / z: 2323.6 m / z: 1743.1 m / z:

[0225] Compound 115 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-NMeQ-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:441) MW (Calculated): 6955.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.8 minutes; m / z:m / 4:1739.6m / 5:

[0226] Compound 116 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:442) MW (Calculated): 6901.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.7 minutes; m / z:m / 4:1726.2m / 5:

[0227] Compound 117 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-V-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:443) MW (Calculated): 6886.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / z:2297.3m / 4:1722.9m / 5:

[0228] Compound 118 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-Aib-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:444) MW (Calculated): 6872.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.5 minutes; m / 3: m / 4: 1718.9 m / 5:

[0229] Compound 119 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-Tle-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:445) MW (Calculated): 6876.7 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 36.0 minutes; m / 3: m / 4: m / 5: 1376.1

[0230] Compound 120 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:446) MW (Calculated): 6973.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.9 minutes; m / 3: 2325.1 m / 4: 1744.6 m / 5:

[0231] Compound 121 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-S-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:447) MW (Calculated): 6859.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 39.8 minutes; m / 3: m / 4: 1715.6 m / 5:

[0232] Compound 122 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-P-E-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:448) MW (Calculated): 7040.9 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 9.3 minutes; m / 3: 2347.9 m / 4: 1761.4 m / 5:

[0233] Compound 123 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-Q-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:449) MW (Calculated): 6931.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.9 minutes; m / 3: 2312.0 m / 4: 1732.4 m / 5:

[0234] Compound 124 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-Q-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:450) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.0 minutes; m / 3:m / 4:m / 5: 1381.0

[0235] Compound 125 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-NMeR-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:451) MW (Calculated): 6955.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.5 minutes; m / 3:m / 4: 1739.8 m / 5:

[0236] Compound 126 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:452) MW (Calculated): 7006.9 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.7 minutes; m / 3:m / 4: 1752.5 m / 5:

[0237] Compound 127 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-E-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:453) MW (Calculated): 6958.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / z: 2320.8 m / 4: 1740.8 m / 5:

[0238] Compound 128 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-D-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:454) MW (Calculated): 6886.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.9 minutes; m / z: m / 4: 1722.3 m / 5:

[0239] Compound 129 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-Aib-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:455) MW (Calculated): 6829.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.0 minutes; m / z: m / 4: 1708.2 m / 5:

[0240] Compound 130 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-I-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:456) MW (Calculated): 6914.8 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 35.4 minutes; m / 3: m / 4: 1729.3 m / 5:

[0241] Compound 131 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-R-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:457) MW (Calculated): 6928.7 Da Synthesis and purification method: S01; P01 LCMS: A01 - B; Rt: 35.4 minutes; m / 3: m / 4: m / 5: 1386.5

[0242] Compound 132 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-I-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:458) MW (Calculated): 6900.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.3 minutes; m / 3: 2301.5 m / 4: 1726.6 m / 5:

[0243] Compound 133 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Tle-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:459) MW (Calculated): 6851.7 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 36.0 minutes; m / 3: m / 4: 1713.4 m / 5:

[0244] Compound 134 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-Q-S-I-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:460) MW (Calculated): 6999.8 Da Synthesis and purification methods: S02; P03 LCMS: A02 - A; Rt: 7.1 minutes; m / 3: 2334.4 m / 4: 1750.9 m / 5:

[0245] Compound 135 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-Y-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:461) MW (Calculated): 6877.7 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 34.2 minutes; m / 3: m / 4: 1720.1 m / 5:

[0246] Compound 136 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-A-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:462) MW (Calculated): 6843.7 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 36.1 minutes; m / 3: m / 4: 1711.7 m / 5:

[0247] Compound 137 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-Tle-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:463) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 35.4 minutes; m / 3: m / 4: 1725.9 m / 5:

[0248] Compound 138 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:464) MW (Calculated): 6785.6 Da Synthesis and purification methods: S02; P03 LCMS: A02 - A; Rt: 7.0 minutes; m / 3: 2262.8 m / 4: 1697.6 m / 5:

[0249] Compound 139 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(SEQ ID NO:465) MW (Calculated): 6856.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / 3: 2286.8 m / 4: 1713.0 m / 5:

[0250] Compound 140 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:466) MW (Calculated): 6945.8 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / 3: 2316.6 m / 4: 1737.6 m / 5:

[0251] Compound 141 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:467) MW (Calculated): 6714.5 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.8 minutes; m / 3: 2239.3 m / 4: 1679.7 m / 5:

[0252] Compound 142 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:468) MW (Calculated): 6986.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.0 minutes; m / z: 2329.8 m / z: 1747.6 m / z:

[0253] Compound 143 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:469) MW (Calculated): 6826.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 6.8 minutes; m / z: 2276.4 m / z: 1707.7 m / z:

[0254] Compound 144 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:470) MW (Calculated): 6730.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.2 minutes; m / z: 2244.5 m / z: 1683.6 m / z:

[0255] Compound 145 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:471) MW (Calculated): 6834.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 9.8 minutes; m / 3: 2279.3 m / 4: 1709.6 m / 5:

[0256] Compound 146 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:472) MW (Calculated): 6859.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.0 minutes; m / 3: 2287.7 m / 4: 1716.0 m / 5:

[0257] Compound 147 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:473) MW (Calculated): 6743.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / 3: 2248.8 m / 4: 1686.9 m / 5:

[0258] Compound 148 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:474) MW (Calculated): 6824.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.8 minutes; m / 3: 2275.9 m / 4: 1707.1 m / 5:

[0259] Compound 149 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:475) MW (Calculated): 6955.8 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.2 minutes; m / 3: 2319.9 m / 4: 1740.0 m / 5:

[0260] Compound 150 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:476) MW (Calculated): 6777.6 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.2 minutes; m / 3: 2260.5 m / 4: 1695.4 m / 5:

[0261] Compound 151 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:477) MW (Calculated): 6843.6 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.9 minutes; m / z: 2281.9 m / z: 1711.8 m / z:

[0262] Compound 152 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:478) MW (Calculated): 6785.6 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.9 minutes; m / z: 2263.3 m / z: 1697.4 m / z:

[0263] Compound 153 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:479) MW (Calculated): 6971.8 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 7.5 minutes; m / z: 2325.0 m / z: 1743.9 m / z:

[0264] Compound 154 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:480) MW (Calculated): 6842.7 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 8.9 minutes; m / 3: 2282.1 m / 4: 1711.6 m / 5:

[0265] Compound 155 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-E-eLys(1,2) (SEQ ID NO 481 and 635 respectively) MW (Calculated): 6826.7 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.6 minutes; m / 3: 2276.8 m / 4: 1707.6 m / 5:

[0266] Compound 156 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:482) MW (Calculated): 6818.6 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / 3: 2273.6 m / 4: 1705.4 m / 5:

[0267] Compound 157 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-OEG-OEG(1,2) (SEQ ID NO:483) MW (Calculated): 6688.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / 3: 2249.8 m / 4: 1687.8 m / 5: 6746.5

[0268] Compound 158 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:484) MW (Calculated): 6816.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.4 minutes; m / 3: 2273.2 m / 4: 1705.2 m / 5:

[0269] Compound 159 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:485) MW (Calculated): 6801.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 6.6 minutes; m / 3: 2268.2 m / 4: 1701.4 m / 5:

[0270] Compound 160 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:486) MW (Calculated): 6746.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 9.8 minutes; m / 3: 2249.8 m / 4: 1687.6 m / 5:

[0271] Compound 161 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:487) MW (Calculated): 6900.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / 3: 2301.2 m / 4: 1726.2 m / 5:

[0272] Compound 162 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(SEQ ID NO:488) MW (Calculated): 6811.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 8.8 minutes; m / 3: 2271.5 m / 4: 1704.1 m / 5:

[0273] Compound 163 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:489) MW (Calculated): 6818.6 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / 3: 2273.8 m / 4: 1705.6 m / 5:

[0274] Compound 164 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2) (SEQ ID NO:490) MW (Calculated): 6956.8 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 8.2 minutes; m / 3: 2319.5 m / 4: 1740.3 m / 5:

[0275] Compound 165 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:491) MW (Calculated): 6885.8 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.8 minutes; m / 3: 2295.9 m / 4: 1722.1 m / 5:

[0276] Compound 166 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:492) MW (Calculated): 6689.5 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.2 minutes; m / 3: 2231.0 m / 4: 1673.6 m / 5:

[0277] Compound 167 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:493) MW (Calculated): 6904.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / 3: 2302.7 m / 4: 1727.3 m / 5:

[0278] Compound 168 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-R-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:494) MW (Calculated): 6969.8 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.9 minutes; m / 3: 2324.9 m / 4: 1743.5 m / 5:

[0279] Compound 169 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:495) MW (Calculated): 6853.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / z: 2285.1 m / z: 1714.0 m / z:

[0280] Compound 170 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:496) MW (Calculated): 6871.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.7 minutes; m / z: 2291.8 m / z: 1719.1 m / z:

[0281] Compound 171 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:497) MW (Calculated): 6705.5 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.1 minutes; m / z: 2236.5 m / z: 1677.6 m / z:

[0282] Compound 172 Y-Aib-E-G-T-F-T-S-D-L-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:498) MW (Calculated): 6850.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.4 minutes; m / z: m / z: 1713.4 m / z:

[0283] Compound 173 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:499) MW (Calculated): 6857.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.0 minutes; m / z: 2286.9 m / z: 1715.5 m / z:

[0284] Compound 174 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:500) MW (Calculated): 6656.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 5.9 minutes; m / z: 2220.1 m / z: 1665.7 m / z:

[0285] Compound 175 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:501) MW (Calculated): 6844.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 8.0 minutes; m / z: 2282.2 m / z: 1712.2 m / z:

[0286] Compound 176 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-E(1,2) (SEQ ID NO 502 and 636 respectively) MW (Calculated): 6714.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / z: 2239.9 m / z: 1679.8 m / z:

[0287] Compound 177 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-OEG-OEG(1,2) (SEQ ID NO 503 and 634 respectively) MW (Calculated): 6859.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.3 minutes; m / z: 2287.1 m / z: 1716.0 m / z:

[0288] Compound 178 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:504) MW (Calculated): 6683.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.7 minutes; m / z: 2228.3 m / z: 1671.5 m / z:

[0289] Compound 179 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-E-E(1,2)(SEQ ID NO 505 and 637 respectively) MW (Calculated): 6843.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.0 minutes; m / z: 2282.2 m / z: 1711.8 m / z:

[0290] Compound 180 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:506) MW (Calculated): 6655.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / z: 2218.6 m / z: 1664.3 m / z:

[0291] Compound 181 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-E-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:507) MW (Calculated): 6772.6 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 36.8 minutes; m / 3: m / 4: 1693.8 m / 5:

[0292] Compound 182 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-Aib-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:508) MW (Calculated): 6848.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.1 minutes; m / 3: m / 4: 1712.9 m / 5:

[0293] Compound 183 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:509) MW (Calculated): 6877.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.4 minutes; m / 3: 2293.2 m / 4: 1720.3 m / 5:

[0294] Compound 184 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Aib-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:510) MW (Calculated): 6822.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.2 minutes; m / 3: m / 4: 1706.5 m / 5:

[0295] Compound 185 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:511) MW (Calculated): 6871.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.3 minutes; m / 3: m / 4: 1718.7 m / 5:

[0296] Compound 186 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-bHGln-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:512) MW (Calculated): 6955.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.0 minutes; m / 3: m / 4: 1739.6 m / 5:

[0297] Compound 187 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:513) MW (Calculated): 6930.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 8.6 minutes; m / z: 2311.2 m / z: 1733.4 m / z:

[0298] Compound 188 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-OEG-OEG(1,2) (SEQ ID NO:514) MW (Calculated): 6730.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.5 minutes; m / z: 2243.9 m / z: 1683.6 m / z:

[0299] Compound 189 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:515) MW (Calculated): 6918.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / z: 2306.7 m / z: 1730.5 m / z:

[0300] Compound 190 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-DArg-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:516) MW (Calculated): 6943.8 Da Synthesis and purification methods: S01; P01 LCMS: A01 - B; Rt: 34.1 minutes; m / 3: m / 4: 1736.6 m / 5:

[0301] Compound 191 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Tle-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:517) MW (Calculated): 6850.7 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 35.4 minutes; m / 3: m / 4: 1713.4 m / 5:

[0302] Compound 192 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-KAc-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:518) MW (Calculated): 6942.8 Da Synthesis and purification methods: S01; P01 LCMS: A01 - B; Rt: 37.0 minutes; m / 3: m / 4: 1736.3 m / 5:

[0303] Compound 193 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:519) MW (Calculated): 6887.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 6.6 minutes; m / z: 2297.1 m / z: 1723.5 m / z:

[0304] Compound 194 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:520) MW (Calculated): 6613.4 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.7 minutes; m / z: 2205.7 m / z: 1654.4 m / z:

[0305] Compound 195 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-L-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:521) MW (Calculated): 6827.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.0 minutes; m / z: m / z: 1707.7 m / z:

[0306] Compound 196 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-E-E-eLys(1,2)(SEQ ID NOs: 522 and 643 respectively) MW (calculated): 6955.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 9.4 minutes; m / z: 2319.1 m / z: 1739.8 m / z:

[0307] Compound 197 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-L-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 523) MW (calculated): 6927.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.7 minutes; m / z: m / z: 1732.4 m / z:

[0308] Compound 198 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO: 524) MW (calculated): 6830.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.4 minutes; m / z: m / z: 1708.3 m / z:

[0309] Compound 199 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-Aib-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:525) MW (Calculated): 6857.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 38.5 minutes; m / 3: m / 4: 1715.2 m / 5:

[0310] Compound 200 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:526) MW (Calculated): 6813.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 6.5 minutes; m / 3: 2272.0 m / 4: 1704.7 m / 5:

[0311] Compound 201 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:527) MW (Calculated): 6963.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 6.9 minutes; m / 3: 2322.1 m / 4: 1742.1 m / 5:

[0312] Compound 202 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:528) MW (Calculated): 6585.4 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.9 minutes; m / 3: 2196.5 m / 4: 1647.5 m / 5:

[0313] Compound 203 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-Y-Y-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:529) MW (Calculated): 6953.8 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.5 minutes; m / 3: 2318.6 m / 4: 1739.0 m / 5:

[0314] Compound 204 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-DAsp-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:530) MW (Calculated): 6902.7 Da Synthesis and purification method: S01; P01 LCMS: A01-B; Rt: 34.6 minutes; m / 3: m / 4: 1726.4 m / 5:

[0315] Compound 205 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:531) MW (Calculated): 6862.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.8 minutes; m / 3: 2288.4 m / 4: 1716.7 m / 5:

[0316] Compound 206 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:532) MW (Calculated): 6928.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.9 minutes; m / 3: 2310.6 m / 4: 1733.1 m / 5:

[0317] Compound 207 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:533) MW (Calculated): 7128.9 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.4 minutes; m / 3: m / 4: 1783.0 m / 5:

[0318] Compound 208 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-bHGln-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:534) MW (Calculated): 6914.8 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 35.1 minutes; m / 3:m / 4:1729.5 m / 5:

[0319] Compound 209 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-L-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:535) MW (Calculated): 6885.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 39.6 minutes; m / 3:m / 4:1722.1 m / 5:

[0320] Compound 210 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-L-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:536) MW (Calculated): 6857.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 37.1 minutes; m / 3:m / 4:1715.2 m / 5:

[0321] Compound 211 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-DAsp-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:537) MW (Calculated): 6930.7 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 35.1 minutes; m / 3: m / 4: 1733.4 m / 5:

[0322] Compound 212 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I- K(1,3)-G-G-P-S-S-G-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:538) MW (Calculated): 6800.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 11.7 minutes; m / 3: 2268.3 m / 4: 1701.3 m / 5:

[0323] Compound 213 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-Aib-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:539) MW (Calculated): 6871.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.5 minutes; m / 3: m / 4: 1718.6 m / 5:

[0324] Compound 214 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:540) MW (Calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.8 minutes; m / z: m / 4: 1725.8 m / 5:

[0325] Compound 215 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:541) MW (Calculated): 6958.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 6.1 minutes; m / z: 2320.6 m / 4: 1740.7 m / 5:

[0326] Compound 216 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-DArg-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:542) MW (Calculated): 6971.8 Da Synthesis and purification methods: S01; P01 LCMS: A01-B; Rt: 34.0 minutes; m / z: m / 4: 1743.7 m / 5:

[0327] Compound 217 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-Y-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:543) MW (Calculated): 7076.9 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.5 minutes; m / z: 2359.6 m / z: 1769.8 m / z:

[0328] Compound 218 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-Aib-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:544) MW (Calculated): 6799.6 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 35.0 minutes; m / z: m / z: 1700.6 m / z:

[0329] Compound 219 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:545) MW (Calculated): 6846.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 11.7 minutes; m / z: 2283.3 m / z: 1712.5 m / z:

[0330] Compound 220 Structure disclosed as SEQ ID NO:546 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:546) MW (calculated): 6941.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 14.5 minutes; m / z: 2314.5 m / z: 1736.1 m / z:

[0331] Compound 221 Structure disclosed as SEQ ID NO:547 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:547) MW (calculated): 6900.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.8 minutes; m / z: m / z: 1725.9 m / z:

[0332] Compound 222 Structure disclosed as SEQ ID NO:548 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-NMeQ-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:548) MW (Calculated): 6956.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.7 minutes; m / z: m / 4: 1740.0 m / 5:

[0333] Compound 223 Structure disclosed SEQ ID NO:549 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:549) MW (Calculated): 6813.6 Da Synthesis and purification methods: S01; L20 LCMS: A01-A; Rt: 6.7 minutes; m / z: 2272.1 m / 4: 1704.5 m / 5:

[0334] Compound 224 Structure disclosed SEQ ID NO:550 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:550) MW (Calculated): 7070.9 Da Synthesis and purification method: S01; P02 LCMS: A01 - B; Rt: 34.4 minutes; m / 3:m / 4:m / 5: 1415.0

[0335] Compound 225 Structure disclosed SEQ ID NO:551 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:551) MW (Calculated): 7029.8 Da Synthesis and purification method: S01; P02 LCMS: A01 - A; Rt: 12.6 minutes; m / 3:m / 4: 1758.2 m / 5:

[0336] Compound 226 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - E - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:552) MW (Calculated): 6886.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 11.6 minutes; m / 3: 2296.6 m / 4: 1722.6 m / 5:

[0337] Compound 227 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-Q-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:553) MW (Calculated): 6999.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.2 minutes; m / z: 2334.1 m / z: 1750.9 m / z:

[0338] Compound 228 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:554) MW (Calculated): 6974.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.7 minutes; m / z: 2326.1 m / z: 1744.6 m / z:

[0339] Compound 229 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:555) MW (Calculated): 6933.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.8 minutes; m / z: 2312.1 m / z: 1734.4 m / z:

[0340] Compound 230 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:556) MW (Calculated): 6855.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.0 minutes; m / 3: m / 4: 1714.6 m / 5:

[0341] Compound 231 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-I-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:557) MW (Calculated): 6860.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.7 minutes; m / 3: m / 4: 1716.0 m / 5:

[0342] Compound 232 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-Y-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:558) MW (Calculated): 6976.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.4 minutes; m / 3: 2326.8 m / 4: 1745.9 m / 5:

[0343] Compound 233 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:559) MW (Calculated): 6982.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 34.6 minutes; m / 3: m / 4: 1746.4 m / 5:

[0344] Compound 234 Y-Aib-E-G-T-F-T-S-D-L-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:560) MW (Calculated): 6892.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 36.4 minutes; m / 3: m / 4: 1723.9 m / 5:

[0345] Compound 235 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:561) MW (Calculated): 6772.6 Da Synthesis and purification methods: S01; L20 LCMS: A01-A; Rt: 6.7 minutes; m / 3: 2259.1 m / 4: 1694.4 m / 5:

[0346] Compound 236 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-NMeR-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:562) MW (Calculated): 6956.8 Da Synthesis and purification methods: S01; P02 LCMS: A01 - B; Rt: 35.7 minutes; m / z: m / z: 1739.9 m / z:

[0347] Compound 237 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-E-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:563) MW (Calculated): 7000.8 Da Synthesis and purification methods: S02; P03 LCMS: A02 - A; Rt: 6.2 minutes; m / z: 2334.9 m / z: 1751.3 m / z:

[0348] Compound 238 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I- K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:564) MW (Calculated): 6643.4 Da Synthesis and purification methods: S01; P02 LCMS: A01 - A; Rt: 13.7 minutes; m / z: m / z: 1661.6 m / z:

[0349] Compound 239 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-E-E-E-E-OEG-OEG(1,2) (SEQ ID NOs: 565 and 638 respectively) MW (calculated): 6845.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.9 minutes; m / z: 2283.0 m / z: 1712.3 m / z:

[0350] Compound 240 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-E-E-E-E-E-eLys(1,2) (SEQ ID NOs: 566 and 639 respectively) MW (calculated): 6812.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.5 minutes; m / z: 2272.1 m / z: 1704.2 m / z:

[0351] Compound 241 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-V-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 567) MW (calculated): 6970.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / z: 2323.8 m / z: 1743.4 m / z:

[0352] Compound 242 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:568) MW (Calculated): 6812.7 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.6 minutes; m / 3: 2272.0 m / 4: 1704.2 m / 5:

[0353] Compound 243 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:569) MW (Calculated): 6684.5 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.8 minutes; m / 3: 2228.7 m / 4: 1672.1 m / 5:

[0354] Compound 244 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-T-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:570) MW (Calculated): 6914.8 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.8 minutes; m / 3: 2306.2 m / 4: 1729.9 m / 5:

[0355] Compound 245 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(SEQ ID NO:571) MW (Calculated): 6898.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 8.6 minutes; m / 3: 2300.5 m / 4: 1725.9 m / 5:

[0356] Compound 246 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:572) MW (Calculated): 6946.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.0 minutes; m / 3: 2316.7 m / 4: 1737.6 m / 5:

[0357] Compound 247 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-I-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:573) MW (Calculated): 6542.3 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.7 minutes; m / 3: m / 4: 1636.4 m / 5:

[0358] Compound 248 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:574) MW (Calculated): 6731.5 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / 3: 2245.0 m / 4: 1684.0 m / 5:

[0359] Compound 249 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-E-E-eLys(1,2) (SEQ ID NO 575 and 643 respectively) MW (Calculated): 6913.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.8 minutes; m / 3: 2305.4 m / 4: 1729.5 m / 5:

[0360] Compound 250 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:576) MW (Calculated): 6656.4 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.0 minutes; m / 3: 2219.5 m / 4: 1664.9 m / 5:

[0361] Compound 251 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:577) MW (Calculated): 6819.6 Da Synthesis and purification methods: S01; L20 LCMS: A01-A; Rt: 6.2 minutes; m / 3: 2274.4 m / 4: 1705.9 m / 5:

[0362] Compound 252 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:578) MW (Calculated): 6785.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 9.8 minutes; m / 3: 2263.0 m / 4: 1697.4 m / 5:

[0363] Compound 253 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:579) MW (Calculated): 6615.4 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.4 minutes; m / 3: m / 4: 1654.7 m / 5:

[0364] Compound 254 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:580) MW (Calculated): 6776.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / 3: 2259.7 m / 4: 1695.0 m / 5:

[0365] Compound 255 Structure disclosed SEQ ID NO:581 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:581) MW (Calculated): 6972.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 6.6 minutes; m / 3: 2325.1 m / 4: 1744.1 m / 5:

[0366] Compound 256 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-P-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO:582) MW (Calculated): 6858.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.2 minutes; m / 3: 2286.9 m / 4: 1715.7 m / 5:

[0367] Compound 257 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-E(1,2) (SEQ ID NOs: 583 and 636 respectively) MW (calculated): 6656.4 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.4 minutes; m / z: 2220.0 m / z: 1665.3 m / z:

[0368] Compound 258 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-I-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2) (SEQ ID NO: 584) MW (calculated): 6832.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.5 minutes; m / z: m / z: 1708.9 m / z:

[0369] Compound 259 Structure disclosed SEQ ID NO: 585 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-S-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 585) MW (calculated): 6872.7 Da Synthesis and purification methods: S02; P03 LCMS: A02 - A; Rt: 6.8 minutes; m / z: 2291.5 m / z: 1719.2 m / z:

[0370] Compound 260 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - AHX(1,2) (SEQ ID NO:586) MW (calculated): 6728.5 Da Synthesis and purification methods: S02; P03 LCMS: A02 - A; Rt: 7.3 minutes; m / z: 2243.7 m / z: 1683.2 m / z:

[0371] Compound 261 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - S - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:587) MW (calculated): 6905.7 Da Synthesis and purification methods: S02; P03 LCMS: A02 - A; Rt: 7.1 minutes; m / z: 2303.4 m / z: 1727.7 m / z:

[0372] Compound 262 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - E - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu(1,2) (SEQ ID NO:588) MW (calculated): 6529.3 Da Synthesis and purification methods: S01; P02 LCMS: A01 - A; Rt: 12.9 minutes; m / z: m / 4: 1633.1 m / 5:

[0373] Compound 263 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - S - E - P - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:589) MW (calculated): 6825.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 12.5 minutes; m / z: 2275.8 m / 4: 1707.2 m / 5:

[0374] Compound 264 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - E - E - E - E - E - E(1,2) (SEQ ID NO 590 and 637 respectively) MW (calculated): 6785.6 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 10.3 minutes; m / z: 2263.0 m / 4: 1697.4 m / 5:

[0375] Compound 265 Structure disclosed SEQ ID NO:591 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:591) MW (calculated): 6913.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 8.9 minutes; m / z: 2305.4 m / z: 1729.3 m / z:

[0376] Compound 266 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:592) MW (calculated): 6688.5 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 10.2 minutes; m / z: 2230.3 m / z: 1673.1 m / z:

[0377] Compound 267 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - gGlu - eLys(1,2) (SEQ ID NO:593) MW (calculated): 6784.6 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 9.3 minutes; m / z: 2263.0 m / z: 1697.2 m / z:

[0378] Compound 268 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu(1,2) (SEQ ID NO:594) MW (calculated): 6527.3 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 10.3 minutes; m / z: 2176.8 m / z: 1632.9 m / z:

[0379] Compound 269 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:595) MW (calculated): 6845.7 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.7 minutes; m / z: 2282.5 m / z: 1712.3 m / z:

[0380] Compound 270 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - Q - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:596) MW (calculated): 6817.6 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 10.1 minutes; m / z: 2273.8 m / z: 1705.2 m / z:

[0381] Compound 271 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - E - F - V - E - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - gGlu(1,2) (SEQ ID NO:597) MW (calculated): 6614.4 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.8 minutes; m / z: 2205.7 m / z: 1654.6 m / z:

[0382] Compound 272 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - A - F - V - E - W - L - I - K(1,3) - G - G - P - E - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - gGlu(1,2) (SEQ ID NO:598) MW (calculated): 6570.3 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.4 minutes; m / z: 2191.6 m / z: 1644.1 m / z:

[0383] Compound 273 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - E - F - V - E - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C20DA - gGlu - gGlu - gGlu - OEG - OEG(1,2) (SEQ ID NO:599) MW (calculated): 6775.6 Da Synthesis and purification method: S02; P03 LCMS: A02 - A; Rt: 7.8 minutes; m / z: 2259.7 m / z: 1694.9 m / z:

[0384] Compound 274 Y - Aib - E - G - T - F - T - S - D - Y - S - I - Aib - L - E - K - Q - A - Q - Aib - E - F - V - E - W - L - I - K(1,3) - G - G - P - S - E - G - A - S - L - R - H - Y - Y - N - W - L - T - R - Q - R - Y - NH2.C18DA - gGlu - gGlu - gGlu - OEG(1,2) (SEQ ID NO:600) MW (calculated): 6602.4 Da Synthesis and purification method: S02; P03 LCMS: A02 - B; Rt: 8.9 minutes; m / z: 2201.8 m / z: 1651.7 m / z:

[0385] Compound 275 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:601) MW (Calculated): 7000.8 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / 3: 2335.4 m / 4: 1751.1 m / 5:

[0386] Compound 276 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:602) MW (Calculated): 6586.3 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / 3: 2196.1 m / 4: 1647.5 m / 5:

[0387] Compound 277 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-bHGln-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:603) MW (Calculated): 6956.8 Da Synthesis and purification method: S01; P02 LCMS: A01-B; Rt: 35.1 minutes; m / 3: m / 4: 1740.0 m / 5:

[0388] Compound 278 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-E-W-L-I- K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:604) MW (calculated): 6847.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.8 minutes; m / 3:m / 4:1712.7m / 5:

[0389] Compound 279 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(SEQ ID NO:605) MW (calculated): 6957.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 8.4 minutes; m / 3:2320.4m / 4:1741.0m / 5:

[0390] Compound 280 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-E-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:606) MW (calculated): 6557.3 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 14.1 minutes; m / 3:m / 4:1640.2m / 5:

[0391] Compound 281 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-Q-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E(1,2)(SEQ ID NOs: 607 and 640 respectively) MW (calculated): 6527.3 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.3 minutes; m / z: 2177.4 m / z: 1632.6 m / z:

[0392] Compound 282 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-OEG-OEG(1,2) (SEQ ID NO:608) MW (calculated): 6489.3 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.5 minutes; m / z: 2163.1 m / z: 1623.1 m / z:

[0393] Compound 283 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-I-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:609) MW (calculated): 6570.4 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 14.0 minutes; m / z: m / z: 1643.5 m / z:

[0394] Compound 284 Structure disclosed SEQ ID NO:610 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-E-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:610) MW (Calculated): 6747.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.1 minutes; m / z: 2249.9 m / z: 1687.7 m / z:

[0395] Compound 285 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-E-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:611) MW (Calculated): 6984.8 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.7 minutes; m / z: 2329.3 m / z: 1747.2 m / z:

[0396] Compound 286 Structure disclosed SEQ ID NO:612 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:612) MW (Calculated): 6942.8 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.7 minutes; m / z: 2315.4 m / z: 1736.7 m / z:

[0397] Compound 287 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:613) MW (calculated): 6846.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.9 minutes; m / z: 2283.2 m / z: 1712.5 m / z:

[0398] Compound 288 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:614) MW (calculated): 7071.9 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 12.9 minutes; m / z: m / z: 1768.6 m / z:

[0399] Compound 289 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:615) MW (calculated): 6685.5 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.6 minutes; m / z: m / z: 1672.2 m / z:

[0400] Compound 290 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(SEQ ID NO:616) MW (calculated): 6813.7 Da Synthesis and purification methods: S01; P02 LCMS: A01-A; Rt: 13.0 minutes; m / 3:m / 4:m / 5: 1363.6

[0401] Compound 291 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E(1,2)(SEQ ID NOs 617 and 640 respectively) MW (calculated): 6657.4 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.6 minutes; m / 3: 2117.4 m / 4: 1633.3 m / 5:

[0402] Compound 292 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:618) MW (calculated): 6657.4 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.6 minutes; m / 3: 2220.6 m / 4: 1665.5 m / 5:

[0403] Compound 293 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:619) MW (Calculated): 6914.7 Da Synthesis and purification method: S02; P03 LCMS: A02-A; Rt: 6.8 minutes; m / 3: 2306.3 m / 4: 1729.9 m / 5:

[0404] Compound 294 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO:620) MW (Calculated): 6528.3 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.5 minutes; m / 3: 2177.2 m / 4: 1633.1 m / 5:

[0405] Compound 295 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO:621) MW (Calculated): 6785.6 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.4 minutes; m / 3: 2262.9 m / 4: 1697.4 m / 5:

[0406] Compound 296 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:622) MW (Calculated): 6786.5 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.1 minutes; m / z: 2263.2 m / z: 1697.7 m / z:

[0407] Compound 297 Structure disclosed SEQ ID NO:623 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:623) MW (Calculated): 6818.6 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.2 minutes; m / z: 2273.9 m / z: 1705.6 m / z:

[0408] Compound 298 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-OEG-OEG(1,2)(SEQ IDNO:624) MW (Calculated): 6689.5 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.6 minutes; m / z: 2230.7 m / z: 1673.3 m / z:

[0409] Compound 299 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(SEQ ID NO:625) MW (calculated): 6689.5 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.4 minutes; m / 3: 2230.9 m / 4: 1673.4 m / 5:

[0410] Compound 300 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-OEG(1,2)(SEQID NO:626) MW (calculated): 6544.4 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 9.3 minutes; m / 3: 2182.3 m / 4: 1637.3 m / 5:

[0411] Compound 301 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(SEQ ID NO:627) MW (calculated): 6798.6 Da Synthesis and purification method: S02; P03 LCMS: A02-B; Rt: 10.4 minutes; m / 3: 2267.1 m / 4: 1700.9 m / 5:

[0412] Compound 302 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-E-E-E-E-E-E(1,2) (SEQ ID NOs: 628 and 637 respectively) MW (calculated): 6786.5 Da Synthesis and purification methods: S02; P03 LCMS: A02-B; Rt: 10.5 minutes; m / z: 2263.1 m / z: 1697.6 m / z:

[0413] Compound 303 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2) (SEQ ID NO: 629) MW (calculated): 6899.7 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / z: 2301.3 m / z: 1726.1 m / z:

[0414] Compound 304 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2) (SEQ ID NO: 630) MW (calculated): 6770.6 Da Synthesis and purification methods: S02; P03 LCMS: A02-A; Rt: 7.2 minutes; m / z: 2258.0 m / z: 1694.0 m / z:

[0415] Compound 305 Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K(1,3)-G-G-P-S-E-G-A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(SEQ ID NO:631) MW (Calculated): 6814.6 Da Synthesis and purification methods: S01; P02 LCMS: A01-B; Rt: 35.5 minutes; m / 3:m / 4:m / 5: 1363.7

[0416] Reference 1 NMeY-Aib-E-G-T-aMeF-T-S-D-K(1,3)-S-I-Aib-L-E-K-Q-R-Q-Iva-E-F-V-R-H-L-L-N-K-Aib-T-R-Q-R-Y-NH2.C16A-G-G-G-G(1,2)(SEQ ID NO 632 and 641 respectively) Example 41 of EP3467106 Solubility: < 1 mg / ml (pH 7)

[0417] Reference 2 NMeY-Aib-E-G-T-aMeF-T-S-D-K(1,3)-S-I-Aib-L-E-K-Q-R-Q-Iva-E-F-V-R-H-L-L-N-K-Aib-T-R-Q-R-Y-NH2.C18DA-G-G-G-G(1,2)(SEQ ID NO 633 and 642 respectively) Example 42 of EP3467106 Solubility: < 1 mg / ml (pH 7)

[0418] Example The following examples illustrate certain specific embodiments of the present invention. Unless otherwise described in detail, the following examples use standard techniques well known and commonly used by those skilled in the art.

[0419] Example 1: hGLP1R / hGIPR / hNPY2R CreLuc Assay in 0.5% and 100% Plasma CHO and HEK-293 recombinant cell lines express the luciferase reporter gene under the control of the cAMP response element (CRE). As a second recombinant protein, GLP-1 and NPY2 receptors are expressed in reporter gene HEK cells, and the GIP receptor is expressed in reporter gene CHO cells. Stimulation of these recombinant cells with agonists leads to an increase in intracellular cAMP levels. In the presence of cAMP, the transcription factor CRE-binding protein (CREB) binds to CRE and CREB-binding protein (CBP), which results in the transcription of the luciferase reporter gene. Using acoustic dispensing on a Labcyte ECHO, peptides serially diluted in 100% DMSO were transferred to 384-well assay plates with 5 μl of pre-dispensed assay buffer (1× HBSS, 20 mM HEPES, pH 7.4, supplemented with 0.5% human plasma). Thawed cryopreserved transgenic reporter gene cells were thawed in the assay buffer. 20 μl (10,000 cells / well) were added to the plates together with the peptides and incubated for 4 hours at 37 °C in a humidified incubator. After incubation, the assay plates were equilibrated to room temperature, followed by the addition of 25 μl of Bright-Glo TM luciferase reagent, incubated for 10 minutes at room temperature and the luminescence was assayed (Envision reader). The concentration-response of the compound was evaluated with 8 peptide concentrations spanning four decades. The EC50 value was calculated using a sigmoidal concentration-response with variable slope by non-linear regression.

[0420] The same assay was performed in the presence of 100% plasma without additional buffer components.

[0421] The results are summarized in Table 3 below. Table 3

[0422] Example 2: Solubility Weigh out the peptide (in the form of TFA salt) in a filter unit (Mini-UniPrep non-needle filter 0.45 μM, Whatman PVDF), and add 0.1 M phosphate buffer at pH 7 to achieve a final peptide concentration of 10 mg / mL. Dissolve the peptide by horizontally shaking the filter unit at 600 rpm for 2 hours at room temperature. Subsequently, filter the sample to remove any insoluble particles. Prepare the control by weighing out the corresponding peptide solid and dissolving it in a suitable medium (such as ACN:H2O) to a final concentration of 1 mg / mL. Analyze both the control and the sample by reverse-phase chromatography. Compare the peak area under the curve of the sample with that of the control, and calculate the solubility based on their ratio. Measure and record the pH for each sample.

[0423] Example 3: Mouse PK Determine the pharmacokinetic parameters of the peptide after intravenous administration to NMRI mice. Male NMRI mice were obtained from Janvier Laboratories (France) and weighed 30 to 40 g. The mice were housed in standard cages with a 12:12 hour light:dark cycle and free access to standard food and water. Dissolve each test peptide in 50 mM phosphate buffer (pH 7.4) / 3.5% mannitol. Perform intravenous administration at 30 to 60 nmol / kg via the tail vein. At different time points up to 56 hours after dosing, collect sequential blood samples from conscious mice from the saphenous vein into vials containing EDTA. Subsequently, prepare plasma by centrifuging at approximately 5000 rpm for 5 minutes and store it at -20 °C until the peptide plasma level is quantified by liquid chromatography-mass spectrometry (LC-MS). Analyze the individual plasma concentration-time profiles by non-compartmental methods and calculate the resulting pharmacokinetic parameters. The mean residence time (MRT) of the GGY peptide according to the present invention has been measured and is summarized in Table 4 (the following table). Table 4

[0424] Example 4: Effect on acute food intake in normal NMRI mice Male NMRI mice at 3 weeks of age were obtained from Janvier (Janvier Labs, France) or from Charles River (Charles River Research Models & Services Germany GmbH). Animals received a microchip (Datamars, Slim Microchip T-SL) for individual identification after delivery. The animals were housed under a 12 / 12 dark-light cycle, 4 mice per cage, and the lights were turned off at 3 pm. The room temperature was controlled to 21 °C + / - 1 °C and the humidity was 60% + / - 20%. Mice had free access to regular rodent food (KLIBA Nafag 3040 or Altromin 1324, Brogaarden, Denmark) and tap water.

[0425] Five days before the start of the study, the animals were newly transferred to the HM2 system (real-time monitoring system for food and water intake) of MBRose in Denmark to adapt to the experimental conditions. Since the animals were uniquely identified by the microchip, each individual animal was identified by its own microchip after entering and leaving the food channel via the antenna. Randomization of the mice in each study group (n = 8; at least 6 weeks of age) was based on food intake (the middle 24-hour interval of the last three days) and body weight before the study was about to start. A vehicle-treated group (50 mM phosphate buffer at pH 7.4 containing 3.5% mannitol) was included in each experiment. To have the same nutritional standard for each animal, food access was locked 8 hours before the dark phase. One hour before night, the animals were treated subcutaneously with the test peptide once. Food intake was reported every hour for a 24-hour period. The food intake was normalized [%] to the average food intake of the vehicle group and the values are summarized in Table 5 (the table below). Table 5

[0426] Item A 1. A polypeptide of the general structure according to formula (I) or a pharmaceutically acceptable salt thereof, Z1-Z2-Z3 (SEQ ID NO: 647) (I), wherein, Z1 is a heteropolypeptide comprising the following amino acid sequence, Y-Aib-X3-G-T-F-T-S-D-X 10 -S-I-X 13 -L-X 15 -X 16 -X 17 -A-X 19 -X 20 -X21 -F-X 23 -X 24 -X 25 -L-X 27 -K(SEQ ID NO:646), wherein X3 is selected to be E or D; X 10 is selected to be Y or L; X 13 is selected to be Aib or L; X 15 is selected to be E, D or A; X 16 is selected to be K, E, D, Aib, G, LysAc, A, L, S, Q or R; X 17 is selected to be Q, E, K or A; X 19 is selected to be Q or E; X 20 is selected to be Aib, D-Asp or D-Arg; X 21 is selected to be A, E or K; X 23 is selected to be V or I; X 24 is selected to be E or Q; X 25 is selected to be W or Y; X 27 is I or L; or Z1 is a derivative thereof having 1 amino acid substitution; Z2 is a linking group comprising the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 wherein X 31 is selected to be P, G or Q; X 32 is selected to be S, E or R; X 33 is selected to be S, E, Y or T; X 34 is selected to be G, P, Y or A; or Z2 is a derivative thereof having 1 amino acid substitution; Z3 is a polypeptide comprising the following amino acid sequence, X 35 -X 36 -X 37 -X 38 -X 39 -Y-X 41 -X 42 -X 43 -X 44 -T-X 46 -X 47 -X 48 -X 49 , wherein X 35 is selected to be A, Q, I, V, E or L; X 36 is selected to be S, E, T, D or L; X 37Selected as L, Aib, V, D-Leu, I or Tle; X 38 Selected as R, L or Aib; X 39 Selected as H, Aib, D-His or Tle; X 41 Selected as Y, L, Aib, I or Tle; X 42 Selected as N or Aib; X 43 Selected as W, H, L, R or Aib; X 44 Selected as L, Aib, D-Arg, D-Asp or Tle; X 46 Selected as R, hArg or D-Arg; X 47 Selected as Q, bh-Gln or NMeQ; X 48 Selected as R or NMeR; X 49 Selected as Y, Tle, Chg, D-Tyr, Phg; or Z3 is a derivative thereof having 1 amino acid substitution. 2. The polypeptide according to item 1, wherein X3 in Z1 is selected as E. 3. The polypeptide according to any one of the foregoing items, wherein X in Z1 10 is selected as Y. 4. The polypeptide according to any one of the foregoing items, wherein X in Z1 13 is selected as Aib. 5. The polypeptide according to any one of the foregoing items, wherein X in Z1 15 is selected as E. 6. The polypeptide according to any one of the foregoing items, wherein X in Z1 16 is selected as K. 7. The polypeptide according to any one of the foregoing items, wherein X in Z1 17 is selected as Q. 8. The polypeptide according to any one of the foregoing items, wherein X in Z1 19 is selected as Q. 9. The polypeptide according to any one of the foregoing items, wherein X in Z1 20 is selected as Aib. 10. The polypeptide according to any one of the foregoing items, wherein X in Z1 21 is selected as A or E, preferably A. 11. The polypeptide according to any one of the foregoing items, wherein X in Z1 23 is selected as V. 12. The polypeptide according to any one of the foregoing items, wherein X in Z1 24 is selected as E or Q, preferably E. 13. The polypeptide according to any one of the foregoing items, wherein X in Z1 25Selected as W. 14. A polypeptide as in any of the preceding items, wherein X in Z1 27 is selected as I. 15. A polypeptide as in any of the preceding items, wherein X in Z2 31 is selected as P. 16. A polypeptide as in any of the preceding items, wherein X in Z2 32 is selected as S. 17. A polypeptide as in any of the preceding items, wherein X in Z2 33 is selected as E or S, preferably S. 18. A polypeptide as in any of the preceding items, wherein X in Z2 34 is selected as G. 19. A polypeptide as in any of the preceding items, wherein X in Z3 35 is selected as A, Q or V, preferably A. 20. A polypeptide as in any of the preceding items, wherein X in Z3 36 is selected as S. 21. A polypeptide as in any of the preceding items, wherein X in Z3 37 is selected as I or L, preferably L. 22. A polypeptide as in any of the preceding items, wherein X in Z3 38 is selected as R. 23. A polypeptide as in any of the preceding items, wherein X in Z3 39 is selected as H. 24. A polypeptide as in any of the preceding items, wherein X in Z3 41 is selected as Y. 25. A polypeptide as in any of the preceding items, wherein X in Z3 42 is selected as N. 26. A polypeptide as in any of the preceding items, wherein X in Z3 43 is selected as W. 27. A polypeptide as in any of the preceding items, wherein X in Z3 44 is selected as L. 28. A polypeptide as in any of the preceding items, wherein X in Z3 46 is selected as R. 29. A polypeptide as in any of the preceding items, wherein X in Z3 47 is selected as Q or NMeQ, preferably Q. 30. A polypeptide as in any of the preceding items, wherein X in Z3 48 is selected as R or NMeR, preferably R. 31. A polypeptide as in any of the preceding items, wherein X in Z3 49 is selected to be Y. 32. A polypeptide as in any of the preceding items, wherein X 35 X 36 X 37 X 38 X 39 is selected to be ASLRH (SEQ ID NO: 645). 33. A polypeptide as in any of the preceding items, wherein X 41 X 42 X 43 X 44 is selected to be YNWL (SEQ ID NO: 326). 34. A polypeptide as in any of the preceding items, wherein X 46 X 47 X 48 X 49 is selected to be RQRY (SEQ ID NO: 327). 35. A polypeptide as in any of the preceding items, wherein the polypeptide is capable of binding and / or activating GLP-1, GIP and hY2 (hNPY2) receptors.

[0427] Item B 1. A polypeptide of the general structure according to formula (I) or a pharmaceutically acceptable salt thereof, Z1-Z2-Z3 (I), wherein, Z1 is a heterologous polypeptide comprising the following amino acid sequence, Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO: 306), or a derivative thereof having 1, 2 or 3 substitutions; Z2 is a linker; Z3 is a polypeptide comprising the following amino acid sequence, A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO: 307) or a derivative thereof having 1, 2, 3, 4 or 5 substitutions. 2. The polypeptide according to Technical Solution 1, wherein the linker is composed of 1 to 10 amino acid residues. 3. The polypeptide according to any of the preceding technical solutions, wherein Z2 has the amino acid sequence GGPSEG (SEQ ID NO: 311) or is a derivative thereof having 1, 2, 3 or 4 amino acid substitutions. 4. The polypeptide as in Technical Solution 3, wherein the 1, 2, 3 or 4 amino acid substitutions in Z2 are present at position X 31 , X 32 , X 33 or X 34 . 5. The polypeptide as in any one of the foregoing technical solutions, wherein Z2 has the amino acid sequence GGX 31 X 32 X 33 X 34 , wherein X 31 is selected from P, G or Q; X 32 is selected from S, E or R; X 33 is selected from S, E or Y; X 34 is selected from G, P, Y or A; or a derivative thereof having 1 amino acid substitution. 6. The polypeptide as in any one of the foregoing technical solutions, wherein 1, 2 or 3 substitutions in the derivative of Z1 are present at amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 23 , X 24 , X 25 or X 27 . 7. The polypeptide as in any one of the foregoing technical solutions, wherein 1, 2, 3, 4 or 5 substitutions in the derivative of Z3 are present at amino acid positions X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 42 , X 43 , X 44 , X 46 , X 47 , X 48 or X 49 . 8. The polypeptide as in any one of the foregoing technical solutions, wherein the derivative of Z3 has 1, 2 or 3 substitutions, preferably 1 or 2 substitutions, most preferably 1 substitution. 9. The polypeptide as in any one of the foregoing technical solutions, wherein the derivative of Z1 has 1 or 2 substitutions, preferably 1 substitution. 10. The polypeptide according to any one of the foregoing technical solutions, wherein one or more substitutions in the derivative of Z1 are selected as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D or A; X 16 is selected as E, D, Aib, G, LysAc, A, L, S, Q or R; X 17 is selected as E, K or A; X 19 is selected as E; X 20 is selected as D-Asp or D-Arg; X 21 is selected as E; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y; X 27 is selected as L. 11. The polypeptide according to any one of the foregoing technical solutions, wherein one or more substitutions in the derivative of Z3 are selected as follows: X 35 is selected as Q, I, V, E or L; X 36 is selected as E, T, D or L; X 37 is selected as Aib, V, D-Leu or I; X 38 is selected as L or Aib; X 39 is selected as Aib, D-His or Tle; X 41 is selected as L, Aib, I or Tle; X 42 is selected as Aib; X 43 is selected as H, L, R or Aib; X 44 is selected as Aib, D-Arg or D-Asp; X 46 is selected as hArg or D-Arg; X 47 is selected as bh-Gln or NMeQ; X 48 is selected as NMeR; X 49 is selected as Tle, Chg, D-Tyr, Phg. 12. The polypeptide according to any one of the foregoing technical solutions, wherein the polypeptide is lipidated at the lysine (K) residue, preferably at the lysine (K) residue at amino acid position X 28 in. 13. The polypeptide according to any one of the foregoing technical solutions, wherein the polypeptide has the general formula L-Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y8 structural esterification, where L is a lipid selected from C18DA or C20DA and additionally where Y 1 -Y 8 each of which is independently selected from: absent, [γE], [OEG], [eLys], or [AHX]. 14. The polypeptide according to any one of the foregoing technical solutions, wherein the lipid is selected from the list consisting of: C18DA, C18DA[γE]-, C18DA[γE][γE]-, C18DA[γE][γE][γE]-, C18DA[γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE][γE][γE]-, C20DA, C20DA[γE]-, C20DA[γE][γE]-, C20DA[γE][γE][γE]-, C20DA[γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE][γE]-, C18DA[eLys], C18DA[γE][eLys]-, C18DA[γE][γE][eLys]-, C18DA[γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][γE][eLys]-, C18DA[γE][γE][γE][γE][γE][γE][eLys]-, C20DA[eLys], C20DA[γE][eLys]-, C20DA[γE][γE][eLys]-, C20DA[γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][eLys]-, C18DA[OEG][OEG]-, C18DA[γE][OEG][OEG]-, C18DA[γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][γE][OEG][OEG]-, C18DA[γE][γE][γE][γE][γE][OEG][OEG]-, C20DA[OEG][OEG]-, C20DA[γE][OEG][OEG]-, C20DA[γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][OEG][OEG]-C20DA[γE][γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG][OEG]-, C18DA[OEG]-, C18DA[γE][OEG]-, C18DA[γE][γE][OEG]-, C18DA[γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][γE][OEG]-, C18DA[γE][γE][γE][γE][γE][γE][OEG]-, C20DA[OEG]-, C20DA[γE][OEG]-, C20DA[γE][γE][OEG]-, C20DA[γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][γE][OEG]-, C18DA[OEG][eLys]-, C18DA[γE][OEG][eLys]-, C18DA[γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][γE][OEG][eLys]-, C18DA[γE][γE][γE][γE][γE][OEG][eLys]-, C20DA[OEG][eLys]-, C20DA[γE][OEG][eLys]-, C20DA[γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][γE][OEG][eLys]-, C18DA[OEG][OEG][eLys]-, C18DA[γE][OEG][OEG][eLys]-, C18DA[γE][γE][OEG][OEG][eLys]-, C18DA[γE][γE][γE][OEG][OEG][eLys]-, C18DA[γE][γE][γE][γE][OEG][OEG][eLys]-, C20DA[OEG][OEG][eLys]-, C20DA[γE][OEG][OEG][eLys]-, C20DA[γE][γE][OEG][OEG][eLys]-,C20DA[γE][γE][γE][OEG][OEG][eLys]-, C20DA[γE][γE][γE][γE][OEG][OEG][eLys]-, C18DA[AHX], C18DA[γE][AHX]-, C18DA[γE][γE][AHX]-, C18DA[γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][γE][AHX]-, C20DA[AHX], C20DA[γE][AHX]-, C20DA[γE][γE][AHX]-, C20DA[γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][γE][AHX]-. 15. The polypeptide according to any one of the foregoing technical solutions, wherein the polypeptide is selected from the group consisting of Compound 1 to Compound 305.

[0428] Item C 1. A polypeptide having the general structure according to formula (I), or a salt or a pharmaceutically acceptable salt thereof, Z1-Z2-Z3 (I), wherein, Z1 is a hybrid polypeptide X1-X consisting of or containing the following amino acid sequence 28 , Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO: 306), or a derivative thereof having 1, 2 or 3 amino acid substitutions; Z2 is a peptide X consisting of or containing the amino acid sequence GGPSEG (SEQ ID NO: 311) 29 -X 34 , or a derivative thereof having 1, 2, 3 or 4 amino acid substitutions; Z3 is a polypeptide X consisting of or containing the following amino acid sequence 35 -X 49 , A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO:307) or a derivative thereof having 1, 2, 3, 4 or 5 amino acid substitutions; Preferably, wherein Z1-Z2-Z3 has 0, 1, 2, 3, 4, 5 or 6 amino acid substitutions. 2. The polypeptide according to item 1, wherein Z1 consists of, comprises or is a derivative of the amino acid sequence Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO:306), and the derivative has 1, 2 or 3 amino acid substitutions at any position among amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 23 , X 24 , X 25 or X 27 , and the one or more substitutions are selected as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D or A; X 16 is selected as E, D, Aib, G, LysAc, A, L, S, Q or R; X 17 is selected as E, K or A; X 19 is selected as E; X 20 is selected as D-Asp or D-Arg; X 21 is selected as E or K; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y; X 27 is selected as L; wherein Z2 consists of, comprises the amino acid sequence GGX 31 X 32 X 33 X 34 , wherein X 31 is selected as P, G or Q; X 32 is selected as S, E or R; X 33 is selected as S, E, Y or T; X 34 is selected as G, P, Y or A; wherein Z3 is composed of the amino acid sequence A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO: 307), or contains the amino acid sequence or is a derivative thereof, and the derivative has 1, 2, 3, 4 or 5 substitutions at any position in amino acid positions X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 42 , X 43 , X 44 , X 46 , X 47 , X 48 or X 49 and the one or more substitutions are selected as follows: X 35 is selected as Q, I, V, E or L; X 36 is selected as E, T, D or L; X 37 is selected as Aib, V, D-Leu, I or Tle; X 38 is selected as L or Aib; X 39 is selected as Aib, D-His or Tle; X 41 is selected as L, Aib, I or Tle; X 42 is selected as Aib; X 43 is selected as H, L, R or Aib; X 44 is selected as Aib, D-Arg, D-Asp or Tle; X 46 is selected as hArg or D-Arg; X 47 is selected as bh-Gln or NMeQ; X 48 is selected as NMeR; X 49 is selected as Tle, Chg, D-Tyr, Phg. 3. The polypeptide according to any one of the preceding items, wherein Z1 is composed of the amino acid sequence Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO: 306), or contains the amino acid sequence or is a derivative thereof, and the derivative has substitutions at amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 23 , X 24, X 25 or X 27 has 1, 2 or 3 amino acid substitutions at any position in 10 10 and the one or more substitutions are selected as follows: X3 is selected as D; X 13 is selected as L; X 15 is selected as L; X 16 is selected as E, D, G, A, S, Q or R; X 17 is selected as E or A; X 19 is selected as E; X 21 is selected as E or K; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y; X 27 is selected as L; where Z2 consists of or contains the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 and X 31 is selected as P or Q; X 32 is selected as S or E; X 33 is selected as S, E, Y or T; X 34 is selected as G, P, Y or A; where Z3 consists of or contains the amino acid sequence A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO:307) or is a derivative thereof, and the derivative has 1, 2 or 3 amino acid substitutions at any position in X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 42 , X 43 , X 44 , X 46 , X 47 , X 48 or X 49 and the one or more substitutions are selected as follows: X 35 is selected as Q, I, V, E or L; X 36 is selected as T; X 37 is selected as Aib, V, I or Tle; X 38 is selected as Aib; X 39 is selected as Tle; X 41 is selected as I, L or Tle; X 44 is selected as Tle; X47 Selected as NMeQ; X 48 Selected as NMeR. 4. A polypeptide as in any of the foregoing items, wherein Z1 consists of, comprises or is a derivative of the amino acid sequence Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO: 306), and the derivative has 1, 2 or 3 amino acid substitutions at any position among X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 21 , X 23 , X 24 or X 25 and the one or more substitutions are selected as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D; X 16 is selected as E, D, G, A, S, Q or R; X 17 is selected as E or A; X 21 is selected as E; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y; wherein Z2 consists of or comprises the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 and X 31 is selected as P or Q; X 32 is selected as S or E; X 33 is selected as S, E, Y or T; X 34 is selected as G, P, Y or A; wherein Z3 consists of, comprises or is a derivative of the amino acid sequence A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO: 307), and the derivative has 1, 2 or 3 amino acid substitutions at any position among X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 44 , X 47 , X 48 or X49 has one or two amino acid substitutions at any position therein, and the one or more substitutions are selected as follows: X 35 is selected from Q, I, V, E or L; X 36 is selected from T; X 37 is selected from Aib, V, I or Tle; X 38 is selected from Aib; X 39 is selected from Tle; X 41 is selected from I, L or Tle; X 44 is selected from Tle; X 47 is selected from NMeQ; X 48 is selected from NMeR. 5. A polypeptide as in any of the foregoing items, wherein Z1 consists of or comprises or is a derivative of the amino acid sequence Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO:306), and the derivative has one or two, preferably one amino acid substitution at any position at amino acid position X 21 or X 24 and the one or more substitutions are selected as follows: X 21 is selected from A or E; X 24 is selected from E or Q; wherein Z2 consists of or comprises the amino acid sequence GGPSEG (SEQ ID NO:311) or GGPSSG (SEQ ID NO:320); wherein Z3 consists of or comprises or is a derivative of the amino acid sequence A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO:307), and the derivative has one or two, preferably one amino acid substitution at any position at amino acid position X 35 、X 37 、X 47 or X 48 and the one or more substitutions are selected as follows: X 35 is selected from Q, V; X 37 is selected from I; X 47 is selected from NMeQ; X 48 is selected from NMeR.

Claims

1. A polypeptide having the general structure according to formula (I), Z1-Z2-Z3 (I) (SEQ ID NO: 647), wherein, Z1 is a heteropolypeptide consisting of the following amino acid sequence, Y-Aib-X3-G-T-F-T-S-D-X 10 -S-I-X 13 -L-X 15 -X 16 -X 17 -A-X 19 -X 20 -X 21 -F-X 23 -X 24 -X 25 -L-X 27 -K(SEQ ID NO:646), wherein X3 is selected to be E or D; X 10 is selected to be Y or L; X 13 is selected to be Aib or L; X 15 is selected to be E, D or A; X 16 is selected to be K, E, D, Aib, G, LysAc, A, L, S, Q or R; X 17 is selected to be Q, E, K or A; X 19 is selected to be Q or E; X 20 is selected to be Aib, D-Asp or D-Arg; X 21 is selected to be A, E or K; X 23 is selected to be V or I; X 24 is selected to be E or Q; X 25 is selected to be W or Y; X 27 is I or L; wherein Z2 is a linker composed of the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 wherein X 31 is selected from P, G or Q; X 32 is selected from S, E or R; X 33 is selected from S, E, Y or T; X 34 is selected from G, P, Y or A; Z3 is a polypeptide consisting of the following amino acid sequence, X 35 -X 36 -X 37 -X 38 -X 39 -Y-X 41 -X 42 -X 43 -X 44 -T-X 46 -X 47 -X 48 -X 49 , where X 35 is selected from A, Q, I, V, E or L; X 36 is selected from S, E, T, D or L; X 37 is selected from L, Aib, V, D-Leu, I or Tle; X 38 is selected from R, L or Aib; X 39 is selected from H, Aib, D-His or Tle; X 41 is selected from Y, L, Aib, I or Tle; X 42 is selected from N or Aib; X 43 is selected from W, H, L, R or Aib; X 44 is selected from L, Aib, D-Arg, D-Asp or Tle; X 46 is selected from R, hArg or D-Arg; X 47 is selected from Q, bh-Gln or NMeQ; X 48 is selected from R or NMeR; X 49 is selected from Y, Tle, Chg, D-Tyr, Phg.

2. The polypeptide according to claim 1, wherein in Z3 X 35 selected from A, E, I, L, Q and V; X 36 selected from S or T; X 37 selected from Aib, I, L, Tle and V; X 38 selected from Aib or R; X 39 selected from H or Tle; X 41 selected from I, L, Tle or Y; X 42 selected from N; X 43 selected from W; X 44 selected from L or Tle; X 46 selected from R; X 47 selected from NMeQ or Q; X 48 selected from NMeR or R; X 49 selected from Y.

3. The polypeptide according to any one of the preceding claims, wherein in Z1 X3 is selected as E or D; X 10 is selected as Y or L; X 13 is selected as Aib or L; X 15 is selected as E or D; X 16 is selected as K, E, D, G, A, S, Q or R; X 17 is selected as Q, E or A; X 19 is selected as E or Q; X 20 is selected as Aib; X 21 is selected as A, E or K; X 23 is selected as V or I; X 24 is selected as E or Q; X 25 is selected as W or Y; X 27 is selected as I or L.

4. The polypeptide according to any one of the preceding claims, wherein Z2 consists of the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 and X 31 is selected from P or Q; X 32 is selected from S or E; X 33 is selected from S, E, Y or T; X 34 is selected from G, P, Y or A; Preferably, wherein Z2 is selected from the group consisting of: GGPEEG (SEQ ID NO: 313), GGPEEP (SEQ ID NO: 314), GGPESG (SEQ ID NO: 315), GGPESP (SEQ ID NO: 316), GGPSEG (SEQ ID NO: 311), GGPSEP (SEQ ID NO: 317), GGPSEY (SEQ ID NO: 318), GGPSSA (SEQ ID NO: 319), GGPSSG (SEQ ID NO: 320), GGPSSP (SEQ ID NO: 321), GGPSSY (SEQ ID NO: 322), GGPSTG (SEQ ID NO: 323), GGPSYG (SEQ ID NO: 324), GGQSSG (SEQ ID NO: 325), GGPRSG (SEQ ID NO: 650), GGPRYY (SEQ ID NO: 651), GGPSYY (SEQ ID NO: 652).

5. The polypeptide according to any one of the preceding claims, Among them, in Z1, X3 is selected as E; X 10 is selected as Y; X 13 is selected as Aib; X 15 is selected as E; X 16 is selected as K; X 17 is selected as Q; X 19 is selected as Q; X 20 is selected as Aib; X 21 is selected as A or E; X 23 is selected as V; X 24 is selected as E or Q; X 25 is selected as W; X 27 is I; wherein Z2 consists of the amino acid sequence GGPSEG (SEQ ID NO: 311) or GGPSSG (SEQ ID NO: 320); Among them, in Z3, X 35 is selected as A, Q or V; X 36 is selected as S; X 37 is selected as I or L; X 38 is selected as R; X 39 is selected as H; X 41 is selected as Y; X 42 is selected as N; X 43 is selected as W; X 44 is selected as L; X 46 is selected as R; X 47 is selected as Q or NMeQ; X 48 is selected as R or NMeR; X 49 is selected as Y.

6. A polypeptide having the general structure according to formula (I), Z1-Z2-Z3 (I), wherein, Z1 is a heterologous polypeptide composed of the amino acid sequences X1-X 28 and Y-Aib-E-G-T-F-T-S-D-Y-S-I-Aib-L-E-K-Q-A-Q-Aib-A-F-V-E-W-L-I-K (SEQ ID NO: 306), or a derivative thereof having 1, 2 or 3 amino acid substitutions; Z2 is a peptide composed of the amino acid sequence X 29 -X 34 and GGPSEG (SEQ ID NO: 311), or a derivative thereof having 1, 2, 3 or 4 amino acid substitutions; Z3 is a polypeptide composed of the amino acid sequence X 35 -X 49 and A-S-L-R-H-Y-Y-N-W-L-T-R-Q-R-Y (SEQ ID NO: 307), or a derivative thereof having 1, 2, 3, 4 or 5 amino acid substitutions.

7. The polypeptide according to claim 6, Among them, in Z1, the 1, 2, or 3 amino acid substitutions are present at amino acid positions X3, X 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 23 , X 24 , X 25 or X 27 at any position, and the one or more substitutions are selected as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D or A; X 16 is selected as E, D, Aib, G, LysAc, A, L, S, Q, or R; X 17 is selected as E, K, or A; X 19 is selected as E; X 20 is selected as D-Asp or D-Arg; X 21 is selected as E or K; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y; X 27 is selected as L; wherein Z2 consists of the amino acids GGX 31 X 32 X 33 X 34 and X 31 is selected from P, G or Q; X 32 is selected from S, E or R; X 33 is selected from S, E, Y or T; X 34 is selected from G, P, Y or A; Among them, in Z3, the 1, 2, 3, 4, or 5 substitutions are present at amino acid position X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 42 , X 43 , X 44 , X 46 , X 47 , X 48 , or X 49 at any position in, and the one or more substitutions are selected as follows: X 35 is selected as Q, I, V, E, or L; X 36 is selected as E, T, D, or L; X 37 is selected as Aib, V, D-Leu, I, or Tle; X 38 is selected as L or Aib; X 39 is selected as Aib, D-His, or Tle; X 41 is selected as L, Aib, I, or Tle; X 42 is selected as Aib; X 43 is selected as H, L, R, or Aib; X 44 is selected as Aib, D-Arg, D-Asp, or Tle; X 46 is selected as hArg or D-Arg; X 47 is selected as bh-Gln or NMeQ; X 48 is selected as NMeR; X 49 is selected as Tle, Chg, D-Tyr, Phg.

8. The polypeptide according to claim 6, Among them, in Z1, the 1, 2 or 3 amino acid substitutions are present at amino acid positions X3, X 10 、X 13 、X 15 、X 16 、X 17 、X 19 、X 20 、X 21 、X 23 、X 24 、X 25 、 or X 27 at any position, and the one or more substitutions are selected as follows: X3 is selected as D; X 10 is selected as L; X 13 is selected as L; X 15 is selected as D; X 16 is selected as E, D, G, A, S, Q or R; X 17 is selected as E or A; X 19 is selected as E; X 21 is selected as E or K; X 23 is selected as I; X 24 is selected as Q; X 25 is selected as Y; X 27 is selected as L; wherein Z2 is composed of the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 and X 31 is selected to be P or Q; X 32 is selected to be S or E; X 33 is selected to be S, E, Y or T; X 34 is selected to be G, P, Y or A; Among them, in Z3, the 1, 2 or 3 substitutions are present at amino acid position X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 42 , X 43 , X 44 , X 46 , X 47 , X 48 or X 49 at any position in, and the one or more substitutions are selected as follows: X 35 is selected as Q, I, V, E or L; X 36 is selected as T; X 37 is selected as Aib, V, I or Tle; X 38 is selected as Aib; X 39 is selected as Tle; X 41 is selected as I, L or Tle; X 44 is selected as Tle; X 47 is selected as NMeQ; X 48 is selected as NMeR.

9. A polypeptide according to any one of the preceding claims, wherein the polypeptide is lipidated at a lysine (K) residue, preferably at the lysine (K) residue at amino acid position X 28 in.

10. A polypeptide according to any one of the preceding claims, wherein the polypeptide is structurally lipidated with the general formula L-Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 wherein L is a lipid selected from 17-carboxy-heptadecanoyl (C18DA) and 19-carboxy-nonadecanoyl (C20DA), and wherein each of Y 1 -Y 8 is independently selected from: absent, [γE], [E], [OEG], [eLys] or [AHX].

11. A polypeptide according to any one of the preceding claims, wherein the polypeptide is structurally lipidated with the general formula L-Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 wherein L is a lipid selected from 17-carboxy-heptadecanoyl (C18DA) and 19-carboxy-nonadecanoyl (C20DA), and wherein each of Y 1 -Y 8 is independently selected from: absent, [γE], [E], [OEG], [eLys] or [AHX], and wherein each of Y 1 -Y 3 is [γE] or Y 1 -Y 3 and each of Y 4 is [E], and wherein Y 5 -Y 8 is independently selected from: absent, [γE], [E], [OEG], [eLys] or [AHX].

12. The polypeptide according to any one of the preceding claims, wherein the polypeptide is selected from the group consisting of Compound 2 to Compound 305 according to Table 3.

13. The polypeptide according to any one of the preceding claims, wherein the polypeptide is in the form of a salt or a pharmaceutically acceptable salt.

14. A polypeptide according to any one of the preceding claims, wherein the polypeptide or a pharmaceutically acceptable salt thereof is comprised in a pharmaceutical composition together with one or more pharmaceutically acceptable carriers and / or excipients.

15. A polypeptide according to any one of the preceding claims, wherein the polypeptide is used as a medicament.

16. A polypeptide according to any one of the preceding claims, wherein the polypeptide is for use in a method of treating and / or preventing: Overweight, long-term weight management, obesity, symptomatic obesity, eating disorders; Insulin resistance, diabetes, type 1 diabetes, type 2 diabetes, prediabetes; Endocrine obesity: Cushing syndrome, hypothyroidism, insulinoma, type 2 diabetes with obesity, pseudohypoparathyroidism, hypogonadism; Endocrine disorders related to obesity: polycystic ovary syndrome (PCOS); Central obesity: hypothalamic obesity, frontal lobe syndrome, Kleine-Levin syndrome; Genetic obesity: Prader-Willi syndrome, Laurence-Moon-Biedl syndrome; Drug-induced obesity: steroid-induced obesity, phenothiazine-induced obesity, insulin-induced obesity, sulfonylurea agent-induced obesity, β-blocker-induced obesity; Comorbidities of obesity and / or overweight: related type 2 diabetes, related hypertension, related NAFLD, related NASH, related DKD, related CKD, related osteoporosis, related sleep apnea, related cancer, related asthma; Hyperlipidemia: hypertriglyceridemia, hypercholesterolemia, high LDL-cholesterolemia, low HDL-cholesterolemia, postprandial hyperlipidemia; Metabolic syndrome: abdominal obesity, hypertension, hyperglycemia, high serum triglycerides, low serum high density lipoprotein (HDL); Liver diseases: metabolic associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), portal hypertension; Cardiovascular diseases: hypertension, atherosclerosis, stroke, heart failure; Kidney diseases: diabetic kidney disease (DKD), chronic kidney disease (CKD); Neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease.

Images