GLP1 / GIP / NPY2 receptor triple agonist

Abstract

Hybrid polypeptides that stimulate GIP, GLP-1, and neuropeptide Y2 (NPY2) receptors and their pharmaceutical uses in the treatment of various diseases, conditions, or disorders, such as obesity, diabetes, and / or NASH, are disclosed. The polypeptides have the general structure Z1-Z2-Z3, where Z1 is a hybrid polypeptide that provides GIP and GLP1R agonism, Z2 is a linker, and Z3 is a polypeptide that provides NPY2R agonism.

Description

[Technical Field]

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

[0002] Overweight and obesity are defined as abnormal or excessive fat accumulation that poses a health risk. 2 A body mass index (BMI) above 30 kg / m is considered overweight 2 A BMI above 100% is considered obese. BMI is calculated based on weight and height. Over the past 50 years, obesity has reached pandemic levels. Globally, obesity has nearly tripled since 1975. In 2016, more than 1.9 billion adults and 340 million children and adolescents were overweight or obese. Both overweight and obesity are major risk factors for numerous chronic diseases, including type 2 diabetes, cardiovascular disease, and cancer, which are leading causes of morbidity and mortality in the United States. Obesity is therefore a serious condition, associated with poor mental health, reduced quality of life, and contributing to shorter life expectancy (Abdelaal 2017). According to the WHO, overweight and obesity are no longer limited to high-income countries but are now rapidly increasing in low- and middle-income countries. WHO's World Health Statistics showed that in 2016, 39% of women and 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 YPIKPEAPREDASPEELNRYYASLRHYLNLVTRQRY (SEQ ID NO: 308) and is present in the mucosa of the gastrointestinal tract, particularly in the endocrine L cells of the ileum and colon. PYY belongs to the pancreatic polypeptide (PP) family, along with neuropeptide Y (NPY) and pancreatic polypeptide (PP). This family of peptides acts on NPY receptors, designated NPY1R (Y1), NPY2R (Y2), NPY4R (Y4), and NPY5R (Y5). This receptor family belongs to the class of G protein-coupled receptors (GPCRs) expressed in the CNS, particularly in the hypothalamic region. The receptors NPY1R-NPY5R exhibit both appetite-suppressing effects (NPY2R, NPY4R) and orexigenic effects (NPY5R, NPY1R). The two main forms of peptide YY are PYY and PYY. 1-36 and PYY 3-36 PYY 1-36 is released from intestinal L cells after a meal in proportion to the amount of energy intake, and a portion is released as PYY 3-36 PYY 3-36 is the major circulating form of PPY and is a relatively selective Y2 receptor agonist. 1-36 and PYY 3-36 PYY inhibits gastric acid secretion, gastrointestinal transit, and food intake. Food intake is inhibited through both its stimulatory effect on Y2 receptors on vagal afferent neurons and its interaction with Y2 receptors in the hypothalamus, consistent with the ability of PYY to increase access to the brain via circumventricular organs, such as the area postrema and subfornical organ. Furthermore, it is known that the blood PPY levels of obese individuals are lower than those of healthy individuals. Therefore, NPY2R and / or NPY4R agonists 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 L cells and K cells of the small intestine, respectively. GLP-1 acts via the GLP-1 receptor and is known to have glucose-dependent insulinotropic activity (i.e., stimulating insulin release) and feeding-suppressive action. GIP acts via the GIP receptor and is also known to have glucose-dependent insulinotropic activity, although its effect on feeding is somewhat unclear. It has been reported that GLP-1 receptor / GIP receptor co-agonist peptides exhibit more potent hypoglycemic and weight-reducing effects than GLP-1 receptor agonists alone. Therefore, research efforts have been made to develop GLP-1 / GIP receptor co-agonists based on the structures of natural glucagon, GIP, or GLP-1 for the treatment of obesity and / or diabetes.

[0005] The most notable effect of GLP-1 agonists is their ability to stimulate insulin secretion in a glucose-dependent manner by binding to GLP-1 receptors expressed in pancreatic beta cells. Almost as importantly, GLP-1 agonists have been shown to inhibit glucagon secretion at glucose levels higher than fasting levels. Importantly, this does not affect the glucagon response to hypoglycemia, making GLP-1 agonists a safe antidiabetic drug with a significantly lower incidence of hypoglycemia compared with insulin. In June 2021, the GLP-1 agonist semaglutide was approved by the FDA for chronic weight management in obese or overweight adults with at least one weight-related condition (e.g., hypertension, type 2 diabetes, or high cholesterol). As anti-obesity drugs, GLP-1 agonists act by binding to GLP-1 receptors in the hypothalamus, thereby suppressing appetite. Furthermore, GLP-1 agonists bind to GLP-1 receptors in the stomach, inhibiting gastric emptying, gastric acid secretion, and gastric motility, and overall increasing satiety. As a result, diabetic subjects treated with GLP-1 receptor agonists often also experience beneficial weight loss in addition to controlling their blood glucose levels.

[0006] However, despite many years of efforts, the number of overweight and obese patients continues to increase. First-line treatments for overweight and obese patients include diet and exercise, but they are often not sufficiently effective. Second-line treatment options are bariatric surgery and drug therapy. Available pharmacological treatments appear to lack efficacy and / or safety, and only a limited number of approved treatments, such as semaglutide, are available in the United States and Europe. Therefore, there remains a high medical demand for more effective and safe treatment options. Future obesity treatments may benefit from simultaneously targeting GLP1-R, GIPR, and NPY2R, taking into account the biological roles of PYY, GIP, or GLP-1. Indeed, recent research efforts in the field of obesity have aimed to develop hybrid polypeptides as triple agonists for these receptors (see, for example, EP3467106 A1). Hybrid polypeptides are highly desirable compared to combination therapies using individual polypeptides for several reasons. First, hybrid polypeptides are easier to formulate into a single dosage unit than mixtures of different polypeptides. This is mainly because different peptides may 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 optimal or compatible with a different polypeptide. Therefore, combination therapy using individual polypeptides may require individual dosage units. Second, hybrid polypeptides are cheaper to produce than individual polypeptides, and regulatory approval is less of a burden.

[0007] The present invention aims to provide hybrid polypeptides that stimulate all receptors, GLP1-R, GIPR and NPY2R, to provide improved treatment of, for example, obesity, diabetes and / or metabolic syndrome. It is a further object of the present invention to provide triple agonists that are soluble at or around physiological pH (eg, pH 7). It is a further object of the present invention to provide triple agonists that have a long duration of action in the body, i.e., a long in vivo half-life. It is a further object of the present invention to provide a triple agonist that stimulates all receptors, GLP1-R, GIPR and NPY2R, and that is soluble at or around physiological pH (e.g., pH 7). It is a further object of the present invention to provide a triple agonist that stimulates all receptors, GLP1-R, GIPR and NPY2R, is soluble at or around physiological pH (e.g., pH 7), and has a long duration of action in the body. It is a further object of the present invention to provide triple agonists that exhibit superior selectivity for the GLP1-R, GIPR, and NPY2R receptors over other incretins or related receptors. For example, the agonists of the present invention may not activate other receptors in the NPY receptor family (e.g., NPY1, NPY4, or NPY5 receptors) and / or GLP-2 or glucagon receptors.

[0008] Summary of the Invention In a first aspect, the present invention provides a polypeptide of the general structure of formula (I), or a pharmaceutically acceptable salt thereof: Z1-Z2-Z3 (I) (In the formula, Z1 is a hybrid polypeptide providing GIPR agonism and GLP1R agonism comprising the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or a derivative thereof having one, two, or three substitutions; Z2 is a linker; Z3 is a polypeptide that provides hY2R agonism and comprises the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or a derivative thereof having one, two, three, four, or five substitutions.

[0009] In a second aspect, the present invention provides a polypeptide comprising the general structure of formula (I), or a pharmaceutically acceptable salt thereof: Z1-Z2-Z3 (SEQ ID NO: 647) (I) (In the formula, Z1 has the amino acid sequence Y-Aib-X3-GTFTSDX 10 -SIX 13 -LX 15 -X 16 -X 17 -AX 19 -X 20 -X 21 -FX 23 -X 24 -X 25 -LX 27 -K (SEQ ID NO: 646), wherein X3 is selected as E or D; 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; X 24 is selected as E or Q; X 25 is selected as W or Y;X 27 is I or L; Z2 has the amino acid sequence GGX 31 -X 32 -X 33 -X 34 where X is a linker consisting of 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 34is selected as G, P, Y or A; Z3 is the amino acid sequence X 35 -X 36 -X 37 -X 38 -X 39 -YX 41 -X 42 -X 43 -X 44 -TX 46 -X 47 -X 48 -X 49 wherein X 35 is selected as A, Q, I, V, E or L; X 36 is selected as S, E, T, D or L; X 37 is selected as L, Aib, V, D-Leu, I or Tle; X 38 is selected as R, L or Aib; X 39 is selected as H, Aib, D-His, or Tle; X 41 is selected as L, Y, Aib, I or Tle; X 42 is selected as N or Aib; X 43 is selected as W, H, L, R or Aib; X 44 is selected as L, Aib, D-Arg, D-Asp, or Tle; X 46 is selected as R, hArg, or D-Arg; X 47 is selected as Q, bh-Gln, or NMeQ; X 48 is selected as R or NMeR; X 49 is selected as Y, Tle, Chg, D-Tyr, Phg.)

[0010] In a third aspect, the invention relates to a polypeptide of the first or second aspect for use as a medicament. In a fourth aspect, the invention relates to a method for the treatment of 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 disease, said method comprising administering to an individual in need thereof a therapeutically effective amount of a polypeptide or a pharmaceutically acceptable salt thereof of the first or second aspect.

[0011] Terms, definitions and conventions Terms not specifically defined herein should be given the meaning that one of ordinary skill in the art would give them in light of the disclosure and context. However, as used herein, unless specified to the contrary, the following terms have the meanings indicated and the following conventions are observed. amino acid According to the present invention, all amino acids are L-amino acids (L-stereoisomers, natural amino acids) unless otherwise stated. In this context, substitutions in analogs / derivatives can be with natural and non-natural amino acids, including L- and D-stereoisomers. Substitutions in derivatives can be conservative substitutions with conservative amino acids. Groups of conservative amino acids can be defined as follows: G, A, V, L, I, P (aliphatic or cyclic), S, C, T, M (hydroxy or sulfur-containing) F, Y, W (aromatic) H, K, R (basic) D, E, N, Q (acid or amide)

[0012] Common unnatural amino acids include NMeG (also referred to as N-methylglycine, NMeGly, MeGly, or sarcosine), meaning the amino acid methylglycine; NMeP (also referred to as N-methyl-L-proline, NMePro, or (S)-1-methylpyrrolidine-2-carboxylic acid), meaning the amino acid methyl-L-proline; Dpr (also referred to as L-2,3-diaminopropionic acid), meaning the amino acid (S)-2,3-diaminopropionic acid; Aib (also referred to as 2-aminoisobutyric acid), meaning the amino acid 2-amino-2-methylpropanoic acid; NMeQ (also referred to as N-methylglutamine, NMeGln, or MeGln), meaning the amino acid N-methyl-L-glutamine; NMeAla (also referred to as N-methylalanine, NMeA, or MeAla), meaning the amino acid (S)-2-amino-3-cyclohexyl Examples of amino acids include Cha (also called L-cyclohexylalanine), which refers to the amino acid (S)-2-amino-3,3-dimethylbutanoic acid; Tle (also called L-2-(tert-butyl)glycine), which refers to the amino acid (S)-2-amino-3-(naphthalen-1-yl)propanoic acid; 1-Nal (also called 3-(1-naphthyl)-L-alanine), which refers to the amino acid (S)-2-amino-3-(naphthalen-1-yl)propanoic acid; Pip (also called L-pipecolic acid), which refers to the amino acid (S)-piperidine-2-carboxylic acid; Nip (also called L-nipecotic acid), which refers to the amino acid (S)-piperidine-3-carboxylic acid; Nle (also called L-norleucine), which refers to the amino acid (2S)-2-aminohexanoic acid; and Phe(4F) (also called 4-fluoro-L-phenylalanine), which refers to the amino acid (S)-2-amino-3-(4-fluorophenyl)propanoic acid.

[0013] Salts and pharmaceutically acceptable salts According to the present invention, the polypeptide or a derivative thereof may be in the form of a salt. According to the present invention, a polypeptide or a derivative thereof may be in the form of a pharmaceutically acceptable salt. Thus, pharmaceutically acceptable salts are intended to include any salts commonly used in the formulation of peptides. Such salts include both acid addition salts and basic salts, examples of which can be found in Remington's Pharmaceutical Sciences, 17th Edition, etc. Similarly, a polypeptide or a pharmaceutically acceptable salt thereof may be in the form of a solvate (e.g., hydrate).

[0014] Compound nomenclature Compounds are represented using Boehringer Ingelheim Line Notation (BILN), a human-readable way of describing complex peptides (Fox et al., J. Chem. Inf. Model. 2022, 62, 17, 3942-3947). In BILN, chains are constructed from monomers (e.g., A for alanine, Aib for isobutyric acid), with two monomers connected by a hyphen "-". Different chains are separated by a dot ".", and the relationship between chains is explicitly defined in parentheses after the monomer. The parentheses include a link ID number and an R group number; for example, K(1,3) represents a lysine residue bound to another monomer with the link ID number "1" via its R "3"-group (ε-amino group). For example, Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYLNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 412) (where C20DA represents 19-carboxynonadecanoyl and gGlu([γE]) represents L-γ-glutamyl) is linked to C20DA via its amino group in the peptide backbone, and to the amino group of the next gGlu via its γ-carboxy group, which is repeated four times, resulting in a total of six gGlu residues, linked to the ε-amino group of lysine (eLys) via the final γ-carboxy group, and to the ε-amino group of lysine (K) via the carboxy group, thus fully defining the following structure: [ka] The structure is disclosed in SEQ ID NO:412.

[0015] Lipidation In the present context, lipidation refers to the covalent attachment of a lipid (L), such as C18DA (octadecanedioic acid), C20DA (icosane diacid) or other half-life extending moiety, to the hybrid polypeptide of the invention, optionally with a linker / spacer (-(Y-) 1-8 The linker / spacer may consist of one or more covalently bonded monomers commonly used in the art, such as [γE], [OEG] or [AHX] shown below. [ka] Lipidation is performed at a lysine residue in the polypeptide (i.e., at the ε (epsilon) amino group) or at the N-terminus, preferably at a lysine residue exemplified herein. Without wishing to be bound by any theory, it is believed that such lipid substituents bind to albumin and other plasma components in the bloodstream, thereby protecting the compounds of the invention from renal filtration and enzymatic degradation. Thus, lipidation is typically performed to improve the pharmacokinetic profile of a polypeptide, for example, by improving metabolic stability, reducing enzymatic degradation, and decreasing excretion and metabolism, and generally shortening the in vivo half-life (t 1 / 2 ) resulting in an extension of the lipid length. The polypeptides of the present invention may be lipidated or non-lipidated based on the desired half-life. When a linker / spacer is present, the lipid (L) is linked to the linker / spacer (-(Y-) 1-8 ) and the polypeptide is covalently attached to one end of a linker / spacer (-(Y-) 1-8 ) (i.e., lipid-linker-peptide). Alternatively, if no linker / spacer is present, the lipid (L) is covalently attached directly to the polypeptide (i.e., lipid-polypeptide). The linker / spacer may comprise 1 to 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 -Y 7 -; or -Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 -), each unit independently selected from, for example, [γE], [OEG] or [AHX], or alternatively selected from, for example, [γE], [E], [OEG], [eLys] or [AHX]. Most preferably, the polypeptide has the general formula LY 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 wherein L is a lipid selected from C18DA or C20DA, and each Y 1 ~Y 8 are independently selected from absent, [γE], [OEG], [eLys], or [AHX], or absent, [γE], [E], [OEG], [eLys], or [AHX].

[0016] The lipid (L) is 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. Thus, it will be understood that preferably the lipid (L) comprises an acyl group, a sulfonyl group, an alkyne, an azide, an N atom, an O atom or an S atom, which form part of the ester, sulfonyl ester, thioester, triazole, amide, amine or sulfonamide. Preferably, the acyl group, or the O or N atom in the lipophilic substituent (L) is linked to the linker / spacer (-(Y-) 1-8 ) to form part of an amide or ester. Similarly, the linker / spacer (-(Y-) 1-8 ) (if present) is attached to an amino acid residue of the hybrid polypeptide of the invention via an ester, sulfonyl ester, thioester, amide, amine or sulfonamide. Thus, preferably, the linker / spacer (-(Y-) 1-8 It will be understood that the linker (-(Y-) ), if present, contains 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 linker (-(Y-) ) 1-8 The acyl group, or O or N atom in ) forms part of an amide or ester with an amino acid residue.

[0017] The lipophilic substituent (L) may comprise a hydrocarbon chain having 10 to 24 carbon atoms, e.g., 14 to 22 carbon atoms, e.g., 16 to 20 carbon atoms. Preferably, it has at least 14 carbon atoms, and preferably 20 or fewer carbon atoms. For example, the hydrocarbon chain may comprise 14, 15, 16, 17, 18, 19, or 20 carbon atoms. The hydrocarbon chain may be linear or branched, saturated or unsaturated. Furthermore, it may comprise a functional group at the end of the hydrocarbon chain, e.g., a carboxylic acid group, a sulfonic acid group, or a tetrazole group. From the above discussion, the hydrocarbon chain is preferably a part of the bond to an amino acid residue of the hybrid polypeptide of the invention, or a linker (-(Y-) 1-8It will also be understood that the hydrocarbon chain may be substituted with a moiety (e.g., an acyl group, a sulfonyl group, an N atom, an O atom, or an S atom) that forms part of the bond to the linker / spacer. Most preferably, the hydrocarbon chain is substituted with an acyl group (for attachment to the linker / spacer), and thus the hydrocarbon chain may be part of an alkanoyl group, such as a dodecanoyl, 2-butyloctanoyl, tetradecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, or eicosanoyl group. The other chain end of these hydrocarbon chains, substituted at one end with an acyl group, may further be functionalized with a carboxylic acid group. Examples of functionalized hydrocarbon chains (e.g., lipophilic substituents L) are 15-carboxyl-pentadecanoyl (briefly, C16DA), 17-carboxy-heptadecanoyl (briefly, C18DA), and 19-carboxy-nonadecanoyl (briefly, C20DA). Preferred lipids or lipid / linkers according to the present disclosure include 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]-, 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]-, C18DA[γE][γE][γE][γE][γE][γE]-, C18DA[γE][γE][γE][γE][γE][γE]-, C18DA[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][γ E][γE]-, C20DA[γE][γE][γE][γE][γE][γE]-, C20DA[γE][γE][γE][γE][γE][γE][γE]-, C1 8DA[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][OEG][eLys]-、C18DA[γE][γE][OEG][eLys]-、C18DA[γE][γE][OEG][eLys]-、C18DA[γE][γE][OEG][eLys]-、C18DA[γE][γE][OEG][eLys]- ]-、C18DA[γE][γE][γE][γE][OEG][eLys]-、C18DA[γE][γE][γE][γE][γE][γE][OEG][eLys]-、C20DA[OEG][eLys]-、C20DA[γE][γE][OEG][eLys]-、C20DA[γE][γE][OEG][eLys]-、C20DA[γE][γE][γE][OEG][eLys]-、C20DA[γE][γE][γE][OEG][eLys]-、C20DA[γE][γE][γE][γE][OEG][eLys]-、C20DA[γE][γE][γE][γE][OEG][eLys]-、C20DA[ 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][OEG][OEG][eLys]-、C18DA[γE][γE][γE][γE][OEG][OEG][eLys]-、C20DA[OEG][OEG][eLys]-、C20DA[γE][ EG][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][γE][AHX]-, C20DA[γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][γE][AHX]-, or C20DA[γE][γE][γE][γE][γE][γE][γE][AHX]-. Preferably, the polypeptide has a structure at amino acid position X, 28 It is lipidated at the lysine (K) residue of

[0018] N- and C-termini In this context, polypeptides are generally amidated at the C-terminus (-CONH2), as in natural peptides. However, polypeptides of the invention may also have a free carboxylic acid (-COOH) or other post-translational modifications, such as a methyl ester (-COOMe). In a highly preferred embodiment of the invention, polypeptides are amidated at the C-terminus. Polypeptides of the invention may have a free amine (-NH2) and may be N-acetylated (-NHCOR), N-methylated (-NHCH3 or -N(CH3)2), deamidated, or N-lipidated at the N-terminus.

[0019] Pharmaceutical Composition In this context, it should be understood that the polypeptide of the present invention, or a pharmaceutically acceptable salt thereof, may be in the form of a pharmaceutical composition. A 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 prior to administration. In some embodiments, the formulation may be a depot formulation providing slow release. It should be understood that various routes of administration may be used based on the choice of formulation and the chemical and / or metabolic stability of the polypeptide. 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. Peptide therapeutics are usually provided as liquid pharmaceutical formulations in pre-filled, ready-to-use syringes. These peptide formulations for subcutaneous administration have been limited in dosage. Therefore, excellent solubility of the peptide at or around physiological pH (e.g., pH 7) is required for administration in ready-to-use syringes.

[0020] Detailed Description of the Invention In a first aspect, the present invention provides a polypeptide of the general structure of formula (I), or a salt thereof, or a pharmaceutically acceptable salt thereof: Z1-Z2-Z3 (I) (In the formula, Z1 is a GIP / GLP1 hybrid polypeptide comprising or consisting of the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or a derivative thereof having one, two, or three amino acid substitutions; Z2 is a linker; Z3 is a polypeptide comprising or consisting of the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO:307), or a derivative thereof having one, two, three, four, or five amino acid substitutions. The compounds of the present invention bind to and / or activate GLP-1, GIP and hY2 (NPY2) receptors.

[0021] Linker Z2 The peptide fragments Z1 and Z3 are connected via a linker Z2. It should be understood that Z1 and Z3 can be connected by various linkers commonly used, for example, in the technical field of fusion proteins. Preferably, the linker comprises or consists of a short peptide consisting of 1 to 10 amino acid residues, for example, 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. Thus, in a preferred embodiment, the linker Z2 is a short peptide consisting of 6 amino acid residues (i.e., amino acid X 29 -X 34 In a more preferred embodiment, Z2 consists of the amino acid sequence GGPSEG (SEQ ID NO: 311, i.e., amino acid X 29 -X 34 ) or a derivative thereof having one, two, three or four amino acid substitutions. Preferably, the one, two, three or four amino acid substitutions in Z2 are at any 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 analog of the amino acid sequence (SEQ ID NO: 311) having one or more amino acid substitutions compared to SEQ ID NO: 311. In a highly preferred embodiment (Z2-Emb1), Z2 (i.e., amino acid X 29 -X 34 ) has the amino acid sequence GGX 31 X 32X 33 X 34 or a derivative thereof having one amino acid substitution, 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 or Y, or preferably S, E, Y or T; X 34 is selected as G, P, Y or A. In further highly preferred embodiments, Z2 has the amino acid sequence of any one of the embodiments of Z2 disclosed below in the second aspect of the invention (eg Z2-Emb2, Z2-Emb3).

[0022] Hybrid polypeptide Z1 Z1 (i.e., amino acids X1-X 28 ) is a GIP / GLP1 hybrid polypeptide comprising or consisting of the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or a derivative thereof having one, two, or three amino acid substitutions. The sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306) (i.e., Z1 in SEQ ID NO: 286) was determined as the reference sequence. Table 1 (see [Table 1-1] onwards) summarizes the number of substitutions in Z1, the positions of Z1 where the substitutions are made, and examples of the amino acids substituted compared to the reference (i.e., SEQ ID NO: 286). As shown in Table 1, amino acid positions X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24, X25, X30, X31, X32, X33, X41, X42, X43, X54, X55, X66, X67, X78, X79, X89, X91, X92, X93, X104, X115, X126, X130, X140, X150, X160, X170, X181, X190, X191, X192, X193, X194, X195, X196, X219, X221, X230, X241, X251, X261, X271, X282, X291, X301, X311, X321, 10 , X 13 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 23 , X 24 , X 25 or X 27has been found to tolerate substitutions. Thus, in a preferred embodiment, one, two or three substitutions in a derivative of Z1 are present at any amino acid position X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24, X25, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36, X37, X38, X40, X41, X42, X43, X44, X45, X56, X57, X58, X59, X60, X61, X62, X63, X64, X75, X85, X96, X107, X118, 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 Preferably, the Z1 derivative has one or two substitutions. Most preferably, the Z1 derivative has one substitution. Thus, the Z1 derivative is a Z1 peptide analog of the amino acid sequence (SEQ ID NO: 306) having one or more amino acid substitutions compared to SEQ ID NO: 306. In a highly preferred embodiment, the substitutions in the derivatives of Z are selected as follows: X is selected as D; 10 is selected as L;X1 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 E or K; X 23 is selected as I;X 24 is selected as Q;X 25 is selected as Y;X 27 is chosen as L.

[0023] Z1 may consist of or comprise the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or may be any amino acid at any amino acid position X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X 10 , X 13 , X 15 , X16 , X 17 , X 19 , X 21 , X 23 , X 24 , X 25 or X 27 and derivatives thereof having one, two or three amino acid substitutions, where 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; 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 chosen as L. Z1 may consist of or comprise the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or may be any amino acid at any amino acid position X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X 10 , X 13 , X 15 , X 16 , X 17 , X 21 , X 23 , X 24 or X 25 and derivatives thereof having one, two or three amino acid substitutions, where 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; X 21 is selected as E;X 23 is selected as I;X 24 is selected as Q;X25 is selected as Y. Z1 may consist of or comprise the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or may contain any amino acid at any amino acid position X 21 or X 24 and derivatives thereof having one or two, preferably one, amino acid substitutions, where the substitutions are selected as follows: X 21 is selected as A or E; X 24 is selected as E or Q.

[0024] Polypeptide Z3 Z3 (i.e., amino acid X 35 -X 49 ) is a polypeptide providing hY2R agonism comprising or consisting of the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or a derivative thereof having one, two, three, four, or five amino acid substitutions. The sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307) (i.e., Z3 in SEQ ID NO: 286) was determined as the reference sequence. Table 1 (see [Table 2-1] et seq.) summarizes the number of substitutions in Z3, the positions of Z3 that may be substituted, and examples of the amino acids substituted compared to the reference (i.e., SEQ ID NO: 286). As shown in Table 1, 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 has been found to tolerate substitutions. Thus, in a preferred embodiment, one, two, three, four or five substitutions in a derivative of Z3 are present at any 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 In a preferred embodiment, Z3 has one, two, or three substitutions. More preferably, Z3 has one or two substitutions. Most preferably, Z3 has one substitution. Thus, the Z3 derivative is a Z3 peptide analog of the amino acid sequence (SEQ ID NO: 307) (i.e., Z3 in SEQ ID NO: 236) having one or more amino acid substitutions compared to SEQ ID NO: 307.

[0025] In a highly preferred embodiment, the substitutions in the derivatives of Z 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, or preferably Aib, V, D-Leu, I or Tle; 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, or preferably 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 the NMeR; X 49 are selected as Tle, Chg, D-Tyr, and Phg. Z3 may consist of or comprise the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or may contain any amino acid at any amino acid position X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 44 , X 47 or X 48 and derivatives thereof having one, two or three amino acid substitutions, where the 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 the NMeR. Z3 may consist of or comprise the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or may contain any amino acid at any amino acid position X 35 , X 37 , X 47 or X 48 and derivatives thereof having one or two, preferably one, amino acid substitutions, where the substitutions are selected as follows: X 35 are selected as Q and V;X 37 is selected as I;X 47 is selected as NMeQ;X 48 is selected as the NMeR. Overall, polypeptides Z1-Z2-Z3 of the first aspect of the invention and of any of the embodiments disclosed herein preferably have 0, 1, 2, 3, 4, 5 or 6 amino acid substitutions, more preferably 0, 1, 2, 3 or 4 amino acid substitutions, and most preferably 0, 1, 2 or 3 substitutions, compared to SEQ ID NO: 286.

[0026] In a second aspect, the present invention provides a polypeptide of the general structure of formula (I), or a salt thereof, or a pharmaceutically acceptable salt thereof: Z1-Z2-Z3 (SEQ ID NO: 647) (I) (In the formula, Z1 has the amino acid sequence Y-Aib-X3-GTFTSDX 10 -SIX 13 -LX 15 -X 16 -X 17 -AX 19 -X 20 -X 21 -FX 23 -X 24 -X 25 -LX 27 X is a GIP / GLP1 hybrid polypeptide comprising or consisting of 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; X 24 is selected as E or Q; X 25is selected as W or Y;X 27 is I or L; Z2 has the amino acid sequence GGX 31 -X 32 -X 33 -X 34 or a derivative thereof having one amino acid substitution, 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; Z3 is the amino acid sequence X 35 -X 36 -X 37 -X 38 -X 39 -YX 41 -X 42 -X 43 -X 44 -TX 46 -X 47 -X 48 -X 49 or a derivative thereof having one amino acid substitution, wherein X 35 is selected as A, Q, I, V, E or L; X 36 is selected as S, E, T, D or L; X 37 is selected as L, Aib, V, D-Leu, I or Tle; X 38 is selected as R, L or Aib; X 39 is selected as H, Aib, D-His, or Tle; X 41 is selected as Y, L, Aib, I or Tle; X 42 is selected as N or Aib; X 43 is selected as W, H, L, R or Aib; X 44 is selected as L, Aib, D-Arg, D-Asp, or Tle; X 46 is selected as R, hArg, or D-Arg; X 47 is selected as Q, bh-Gln, or NMeQ; X 48is selected as R or NMeR; X 49 is selected as Y, Tle, Chg, D-Tyr, Phg.)

[0027] Preferred amino acids in Z1 In a preferred embodiment (Z1-Emb1), 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; Alternatively, Z1 is a derivative thereof having one amino acid substitution.

[0028] In a preferred embodiment (Z1-Emb2), 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 chosen as Q; X 20 is selected as Aib; X 21 is selected as A or E; 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 I; Alternatively, Z1 is a derivative thereof having one amino acid substitution.

[0029] In a preferred embodiment (Z1-Emb3), X3 is selected as E; X 10 is selected as Y; X 13 is selected as Aib; X 15 is chosen as E; X 16 is chosen as K; X 17 is chosen as Q; X 19 is chosen as Q; X 20 is selected as Aib; X 21 is selected as A or E; X 23 is chosen as V; X 24 is selected as E or Q; X 25 is chosen as W; X 27 is I; Alternatively, Z1 is a derivative thereof having one amino acid substitution.

[0030] In a preferred embodiment, X3 in Z1 is selected as E. In a preferred embodiment, X in Z1 is selected as E. 10is selected as Y. In a preferred embodiment, X in Z1 13 is selected as A. In a preferred embodiment, X in Z is 15 is selected as E. In a preferred embodiment, X in Z 16 is selected as K. In a preferred embodiment, X in Z 17 is selected as Q. In a preferred embodiment, X in Z1 19 is selected as Q. In a preferred embodiment, X in Z1 20 is selected as A. In a preferred embodiment, X in Z is 21 is selected as A. In a preferred embodiment, X in Z1 23 is selected as V. In a preferred embodiment, X in Z1 24 is selected as E. In a preferred embodiment, X in Z 25 is selected as W. In a preferred embodiment, X in Z1 27 is chosen as I. In a highly preferred embodiment, X3 in Z1 is selected as E; 10 is chosen as Y; X in Z1 13 is selected as A. In a highly preferred embodiment, X in Z is 15 is chosen as E; X in Z1 16 is chosen as K; X in Z1 17 is selected as Q. In a highly preferred embodiment, X in Z1 19 is chosen as Q; X in Z1 20 is chosen as Aib; X in Z1 21 is selected as A. In a highly preferred embodiment, X in Z1 23 is chosen as V; X in Z1 24 is chosen as E; X in Z1 25 is chosen as W; X in Z1 27 is chosen as I.

[0031] Preferred amino acids in Z2 In a preferred embodiment (Z2-Emb1), Z2 has the amino acid sequence GGX 31 X 32 X 33 X 34 or a derivative thereof having one amino acid substitution, 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. In a preferred embodiment (Z2-Emb2), Z2 has the amino acid sequence GGX 31 -X 32 -X 33 -X 34 or a derivative thereof having one amino acid substitution, 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. 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 a derivative thereof having one amino acid substitution. In a preferred embodiment, X in Z 31 is selected as P. In a preferred embodiment, X in Z2 32 is selected as S. In a preferred embodiment, X in Z2 33 is selected as S. In a preferred embodiment, X in Z2 34 is chosen as G.

[0032] In a further 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), GGPSEG (SEQ ID NO: 313), GGPSEP (SEQ ID NO: 314), GGPSEG (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), GGPSEG (SEQ ID NO: 313), GGPSEG (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: 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). In a further 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).

[0033] In a further 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). In a further 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).

[0034] Preferred amino acids in Z3 In a further embodiment (Z3-Emb1), X 35 are selected as A, E, I, L, Q and V; X 36 is selected as S or T; X 37 are selected as Aib, I, L, Tle and V; X 38 is selected as Aib or R; X 39 is selected as H or Tle; X 41 is selected as I, L, Tle or Y; X 42 is chosen as N; X 43 is chosen as W; X 44is selected as L or Tle; X 46 is selected as R; X 47 is selected as NMeQ or Q; X 48 is selected as NMeR or R; X 49 is selected as Y; Alternatively, Z3 is a derivative thereof having one amino acid substitution.

[0035] In a preferred embodiment (Z3-Emb2), X 35 is selected as A, Q or V; X 36 is chosen as S; X 37 is selected as I or L; X 38 is selected as R; X 39 is chosen as H; X 41 is selected as Y; X 42 is chosen as N; X 43 is chosen as W; X 44 is chosen 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; Alternatively, Z3 is a derivative thereof having one amino acid substitution.

[0036] In a preferred embodiment, X in Z 35 is selected as A. In a preferred embodiment, X in Z3 36 is selected as S. In a preferred embodiment, X in Z3 37is 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 Z 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.

[0037] In a highly preferred embodiment, X 35 X 36 X 37 X 38 X 39 is selected as ASLRH (SEQ ID NO: 645). In a highly preferred embodiment, X 41 X 42 X 43 X 44 is selected as YNWL (SEQ ID NO: 326). In a highly preferred embodiment, X 46 X 47 X 48 X 49 is selected as RQRY (SEQ ID NO: 327). It should be understood that the second aspect of the invention and / or any related embodiment disclosed herein may depend on the first aspect of the invention and / or any related embodiment disclosed herein. It should be understood that one or more embodiments of the first or second aspect of the invention describing preferred amino acids at position Z1 may be combined with one or more embodiments describing preferred amino acids at positions Z2 and / or Z3, and vice versa. Thus, any combination of one or more embodiments referred to under "Preferred amino acids at Z1" may be combined with one or more embodiments referred to under "Preferred amino acids at Z2" and / or "Preferred amino acids at Z3," and vice versa. Any such combination of embodiments is to be understood as a direct and explicit part of the present disclosure.

[0038] With respect to the second aspect of the present invention, examples of combinations of the above-mentioned embodiments are: Z1-Z2-Z3 of the second embodiment, 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.

[0039] Preferred lipids / linkers The polypeptides of the first and / or second aspect of the invention may comprise a lysine (K) residue, preferably at amino acid position X 28 In the case of lysine (K) residues in 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 (briefly, C18DA) and 19-carboxy-nonadecanoyl (briefly, C20DA), and further wherein each Y1 ~Y 8 are independently selected from absent, [γE], [E], [OEG], [eLys], or [AHX]. Preferably, the lipid / linker has the general formula LY 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 wherein L is a lipid selected from C18DA or C20DA, and each Y 1 ~Y 8 are independently selected from [γE], [E], [OE G], [eLys], or [AHX], and each Y 1 ~Y 3 is [γE], or each Y 1 ~Y 3 is [E] and Y 4 is selected from [γE], [E] or [OEG], and each Y 5 ~Y 8 are independently selected from absent, [γE], [E], [OEG], [eLys], or [AHX]. Preferably, the lipid / linker has the general formula LY 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 wherein L is C20DA and each Y 1 ~Y 8 are independently selected from [γE], [E], [OE G], or [eLys], and each Y 1 ~Y 4 is [γE], or each Y 1 ~Y 4 is [E] and Y 5 is selected from [γE], [E], [OEG] or [eLys], and each Y 6 ~Y 8 are independently selected from absent, [γE], [E], [OEG], or [eLys].

[0040] The polypeptides of the present invention may be, for example, 28 and the lipid / linker is C18DA[E][E][E][E]-(Sequence number: 640), C18DA[E][E][E][E][E]-(Sequence number: 636), C18DA[E][E][E][E][E][E]-(Sequence number: 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]-(Sequence number: 635), C18DA[E][E][E][E][E][E][eLys]-(Sequence number: 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]-(Sequence number: 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]-(Sequence number: 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]-(Sequence number: 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][γ E][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][eLy s]-, C18DA[γE][γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][γE][AHX]-, C18DA[γE][γE][γE][γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][γE][AHX]-, or C20DA[γE][γE][γE][γE][γE][γE][γE][AHX]-.

[0041] The polypeptides of the present invention may be, for example, 28 and the lipid / linker is 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][eLy s][eLys]-, C20DA[E][E][E][E][OEG][OEG]-(SEQ ID NO: 638), C20DA[γE][γE][γE][γE][OEG][OEG]-, C2 0DA[γE][γE][γE][γE][γE][OEG][OEG]-, C20DA[γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][ γE][γE][γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][γE][OEG]-, C20DA[γE][γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][γE][γE][OEG][eLys]-, C20DA[γE][γE][γE][γE][γE][OEG][OEG][eLys]-.

[0042] The triple agonists of the present invention are generally soluble at a pH of around 7. There are several techniques known to those skilled in the art for measuring solubility. Preferably, the solubility of the peptides of the present invention is determined as disclosed in Example 2 below. In some embodiments, the solubility of the compounds of the present invention is 1.0 mg / ml or greater at a pH of about 7. In some embodiments, the solubility of the compounds of the present invention is greater than 3.0 mg / ml at around pH 7. In some embodiments, the solubility of the compounds of the present invention is greater than 5.0 mg / ml at around pH 7. In some embodiments, the solubility of the compounds of the present invention at a pH of about 7 is 6.0 mg / ml or more, 7.0 mg / ml or more, 8.0 mg / ml or more, or 9.0 mg / ml or more.

[0043] The hybrid polypeptides of the present invention are capable of stimulating hGLP1R, GIPR, and hNPY2R in the presence of human serum albumin, a major protein present in human plasma (see Table 3). The activity of the peptides of the present invention in the presence of human plasma is an important prerequisite for promising compounds that are useful in treating the disclosed diseases. Those skilled in the art will be aware of suitable assay formats, and examples are provided below. For example, the EC values ​​for the peptides of the present invention against hGLP1R, GIPR, and hNPY2R in the presence of 100% human plasma (100% hP) were: 50 Values ​​were assessed by the assay described in Example 1 below. In some embodiments of the peptides of the invention, the EC 50 is less than 100 nM (e.g., 0.01 nM to 100 nM) and the EC 50 is less than 1000 nM (e.g., 0.01 nM to 1000 nM). In some embodiments of the peptides of the invention, the EC 50 is 30 nM or less (e.g., 0.01 nM to 50 nM), and the EC 50 is less than 300 nM (e.g., 0.01 nM to 300 nM). In some embodiments of the peptides of the invention, the EC 50 is 10 nM or less (e.g., 0.01 nM to 10 nM), and the EC 50 is less than 100 nM (e.g., 0.01 nM to 100 nM).

[0044] In a preferred embodiment of the peptide of the present invention, the EC 50 is 10 nM or less (e.g., 0.01 nM to 10 nM), and the EC 50 is less than 100 nM (eg, 0.01 nM to 100 nM) and has a solubility of 1.0 mg / ml or more at around pH 7. In some embodiments, the peptides of the invention have advantageous pharmacokinetic properties, in that the in vivo half-life of the peptides of the invention is greater than 6 hours, greater than 8 hours, or greater than 10 hours in mice (NMRI mice, see measurements described in Example 3). In a preferred embodiment of the peptide of the present invention, the EC 50 is 10 nM or less (e.g., 0.01 nM to 10 nM), and the EC 50 has a solubility of 1.0 mg / ml or more at a pH of around 7, and an in vivo half-life of more than 8 hours.

[0045] In a third aspect, the present invention provides polypeptides for use as pharmaceuticals. Because the Y2 receptor has an appetite-suppressing effect, polypeptides having Y2 agonist activity may be useful in treating symptoms associated with eating disorders, obesity (e.g., simple obesity or symptomatic obesity), and / or diabetes. Furthermore, the gastrointestinal hormones GLP-1 and GIP (called incretins) promote insulin secretion from the pancreas. Because incretins are closely related to glucose metabolism, polypeptides having GLP-1 receptor agonist activity and GIP receptor agonist activity may be useful in treating symptoms associated with glucose metabolism disorders, including diabetes and obesity. Therefore, the polypeptides of the present invention may have an appetite-suppressing effect and / or weight-reducing effect. In a preferred embodiment, the present invention provides a method for treating symptoms associated with excessive weight (overweight), obesity, (e.g., simple obesity (chronic 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 cholesterol, low HDL cholesterol, postprandial hyperlipidemia), metabolic syndrome (three of the following five conditions: abdominal obesity, hypertension, hyperglycemia, high serum triglycerides, and low serum high-density lipoprotein (HDL)), liver disease, e.g., metabolically associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NALHD), and neurodegenerative diseases (Alzheimer's disease or Parkinson's disease), but also other obesity-related diseases, disorders or symptoms selected from the list consisting of obesity-associated diseases such as osteoporosis, sleep apnea, obesity-associated cancer, and obesity-associated asthma.Examples of syndromic obesity include endocrine obesity (e.g., Cushing's 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, Klein-Levin syndrome), genetic obesity (e.g., Prader-Willi syndrome, Laurence-Moon-Biedl syndrome), and drug-induced obesity (e.g., steroid-induced obesity, phenothiazine-induced obesity, insulin-induced obesity, sulfonylurea-induced obesity, beta-blocker-induced obesity). The polypeptides of the present invention may also be used to prevent obesity, or to prevent or reversal of comorbidities of obesity and / or overweight, such as type 2 diabetes, hypertension, NAFLD, NASH, DKD, CKD, sleep apnea, obesity-associated cancer or obesity-associated asthma.

[0046] In a fourth aspect, the present invention provides a method for the treatment of a disease, disorder and / or condition, said method comprising administering a therapeutically effective amount of a polypeptide or a pharmaceutically acceptable salt thereof of any aspect and embodiment disclosed herein to a human in need thereof. Preferably, the disease, disorder and / or condition is selected from the list consisting of overweight, obesity, diabetes (type 1 or type 2) or pre-diabetes, eating disorders, hyperlipidemia, metabolic syndrome, NAFLD, NASH, and / or cardiovascular disease. Most preferably, the disease, disorder and / or condition is obesity, pre-diabetes and / or diabetes (type 1 or type 2). The present invention further provides a method of binding to and / or activating GLP-1, GIP and hNPY2 receptors in a human in need thereof, said method comprising administering a therapeutically effective amount of a polypeptide or a pharmaceutically acceptable salt thereof of any aspect and embodiment disclosed herein.

[0047] Similarly, the invention relates to the use of a polypeptide or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of a disease, disorder and / or condition of any of the aspects and embodiments disclosed herein. The weekly dose range of the polypeptides of the general structure of formula (I) that can be administered is typically between 0.01 and 100 mg (subcutaneously) for humans. The polypeptides of the invention may be administered subcutaneously using a suitable device, for example, a pre-filled, ready-to-use injector, syringe, pen injector, or auto-injector. The actual pharmaceutically effective 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 specific condition. [Example]

[0048] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10] [Table 1-11] Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16 Table 1-17 Table 1-18 Table 1-19

[0049] Table 2-1 Table 2-2 Table 2-3 Table 2-4 Table 2-5 Table 2-6 Table 2-7 Table 2-8 [Table 2-9] [Table 2-10]

[0050] General Procedure for Solid Phase Synthesis of Peptides All peptides were synthesized by standard Fmoc-based solid-phase peptide chemistry on Tentagel S RAM resin (loading 0.23-0.25 mmol / g, bead size 90 μm) supplied by Iris Biotech GmbH or Rapp Polymere GmbH. The following protected amino acids were 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, Fm 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, the L-form of the amino acid building blocks was utilized. Modular half-life extension moieties were assembled by solid phase peptide synthesis (SPPS) using protected building blocks such as, 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.

[0051] Fmoc-Glu-OtBu, Oxyma, and DIC amino acids were purchased from standard suppliers, such as Bachem, Novabiochem, ABCR GmbH & CO. KG., Iris Biotech GmbH, and 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. Peptide assembly was performed by stepwise chain elongation toward the N-terminus of each sequence, starting from the C-terminus, until the N-terminal amino acid was reached. After deprotection of the side chains of branched amino acids, e.g., Lys(Dde), assembly of the half-life extension moiety was performed. The peptides were obtained as TFA salts after cleavage / deprotection or after HPLC purification. The trifluoroacetate can be exchanged by standard procedures (e.g., resin-ion exchange procedures), as disclosed, for example, in Roux, St. et al. J. Pept. Sci. 2008; 14: 354-359.

[0052] 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 on a 0.25 mmol scale using a CEM Liberty Blue Peptide Synthesizer. The stoichiometry and concentrations for the peptide coupling reaction were 4 equivalents of appropriately protected amino acid in DMF (0.2 mol / L, 5 ml), 4 equivalents of oxime in DMF (1 mol / L, 1 ml), and 8 equivalents of DIC in DMF (1 mol / L, 2 ml). Reaction times and temperatures varied for each amino acid. Single couplings at 90°C for 4 min were used for all standard amino acids except for those mentioned below. Single couplings at 75°C for 20 min were used for Fmoc-Aib-OH, and the amino acid after Aib was coupled twice. Double couplings at 90°C for 4 min were used for Fmoc-Arg(Pbf)-OH, C18DA(tBu), C20DA(tBu), Fmoc-OEG-OH, FmocNMeArg(Pbf)-OH, and Fmoc-NMeGln(Trt)-OH. The amino acids after NMeArg and NMeGln were coupled twice. The final eight standard amino acids in the backbone were coupled at 90°C for 8 min. Capping steps were performed with 20% acetic anhydride in DMF (10 ml) at 65 °C for 5 min before and after the coupling of Fmoc-Glu-OtBu and before the coupling of C18DA(tBu) and C20DA(tBu). αFmoc deprotection was carried out using 10% piperidine / DMF (10 ml) at 90°C for 1 minute. Deprotection of the Lys(Dde)-site was carried out using 5% hydrazine hydrate in DMF (10 ml) at 90°C for 3 minutes, and this deprotection was carried out twice. The raw material was washed with DCM on the resin and dried before cleavage. Cleavage from the resin and deprotection were carried out using a mixture of 95% TFA / water (10 ml) and triisopropylsilane (250 μl) at 40°C for 45 minutes. The crude peptide was precipitated with cold tert.butyl-methyl ether, dissolved in 50% acetonitrile / water, and purified by preparative HPLC.

[0053] Synthesis method 2 (S02) Peptides were synthesized by SPPS on a 0.2 mmol scale using a MultiSynTech SYRO. Standard amino acid coupling was achieved using 4 equivalents (0.5 mol / L) of an appropriately protected amino acid dissolved in 0.5 mol / L Oxymer-DMF solution and 4.5 equivalents (1 mol / L) of DIC in DMF. Fmoc-Phe-OH was dissolved in 0.5 mol / L Oxymer-NMP, and 4 equivalents were used for coupling (0.5 mol / L). The coupling time for the first 23 amino acids, starting from the C-terminus, was 15 min at 75 °C (Cys and His were coupled at 50 °C). Further elongation was performed by double coupling (2 x 15 min at 75 °C). Deprotection of the Lys(Mtt) moiety was selectively performed using hexafluoroisopropanol (10 min x 10, 10 ml at room temperature). Derivatization of the deprotected lysine intermediate was carried out by double coupling of 4 equivalents of the appropriate linker building block (Fmoc-OEG-OEG-OH, Fmoc-Glu-OtBu, Boc-Lys(Fmoc)-OH, C18DA(tBu), C20DA(tBu)) at 75 °C for 15 min. αFmoc deprotection was carried out using 40% piperidine in NMP (4 ml) for 3 min, followed by 20% piperidine in NMP (4 ml) for 15 min at 45 °C. Appropriately protected Fmoc-Asp, Fmoc-Cys, and Fmoc-His intermediates were deprotected at room temperature. The peptides were cleaved from the resin and side-chain deprotected by adding 15 ml of TFA / DODT / TES / water (95:2:1:2) for 4 h at room temperature or 60 min at 45 °C. The peptides were precipitated with cold diethyl ether, dissolved in acetonitrile / water, and purified by preparative HPLC (Purification Method 3, P02).

[0054] 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 equipped with preparative pumps G7161B, G7111B, and G7110B, a diode array detector G7115A, a mass spectrometer G6135B, and a fraction collector G7158B. A Waters Luna Prep C8(3) column (100 Å, 10 μm, 300 g, self-packed steel column) was used as the stationary phase. The mobile phase was a gradient of Buffer A (ACN) and Buffer (H2O + 0.1% TFA) as listed in the table below, at a flow rate of 150 ml / min at 40 °C. Appropriate fractions were pooled and lyophilized. The final product was characterized by analytical HPLC-MS (U046_001 and U046_006).

[0055] [Table 3]

[0056] 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 equipped with an AP-MOD preparative pump (maximum flow rate: 200 ml / min), an ECOM Flash 10 diode array detector, and a GILSON GX 281 fraction collector. The stationary phase was a Phenomenex LUNA C8 10 μm preparative column (50 × 250 mm). The peptide was eluted with a focused gradient using water (eluent A) and acetonitrile (eluent B) at a flow rate of 120 ml / min at 40 °C; modifier solutions were added in "at-column dilution" mode to maintain a constant amount of 0.1% TFA in the mobile phase. Homogeneous fractions were pooled and lyophilized. The final product was characterized by HPLC-MS (U046_001 and U046_006).

[0057] [Table 4]

[0058] Purification method 3 (P03) The crude peptide was purified by reverse-phase HPLC using a Waters preparative HPLC system equipped with a C8 column (Reprosil Gold 200 Å, 5 μm, 40 mm × 250 mm), a preparative pump (Waters 2545), a UV / VIS detector (Waters 2489), and a Waters fraction collector III. The mobile phase consisted of a gradient of buffer A (0.1% TFA in HO) and buffer B (0.1% TFA in ACN, gradient: 35–45% B over 20 min) at a flow rate of 50 ml / min at room temperature. Appropriate fractions were analyzed, pooled, and lyophilized. The final product was characterized by analytical UPLC-MS (A02).

[0059] Analysis method 1 (A01-A / B) The purity and mass of the peptides were estimated by analytical HPLC-MS using an Agilent 1260 HPLC system equipped with a mass detector G6135, using a Kinetex C8 column (4.6 mm x 150 mm, 2.6 μm, Phenomenex). Analysis was performed by gradient elution with buffer A (0.3% TFA in HO) and buffer B (0.24% TFA in ACN) at a temperature of 40°C. Details of the gradient and flow rates are summarized in the table below. Retention times and masses were recorded. The purity of the peptides (relative peak area at 214 nm) ranged from 80 to 99%, preferably above 95%.

[0060] [Table 5]

[0061] [Table 6]

[0062] Analysis method 2 (A02-A / B) The purity and mass of the peptides were determined by analytical HPLC-MS using a Kinetex C8 column (Phenomenex, 100 Å, 2.6 μm, 4.6 mm × 150 mm) on a Waters Acquity HPLC system equipped with a 3100 mass detector. Analysis was performed by gradient elution with buffer A (0.3% TFA in HO) and buffer B (0.3% TFA in ACN) at a temperature of 40°C. Details of the gradient and flow rates are summarized in the table below. Retention times and masses were recorded.

[0063] [Table 7]

[0064] [Table 8]

[0065] 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-butoxycarbonyl Chg: Cyclohexyl-glycine C18DA(tBu): 18-(tert-butoxy)-18-oxooctadecanoic acid C20DA(tBu): 20-(tert-butoxy)-20-oxoicosanoic 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-dioxa-1,8-octanedithiol DPBS: Dulbecco's phosphate buffered saline D-Tyr: D-tyrosine eLys: N-epsilon-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-gamma-L-glutamate hArg: homo-L-arginine HTRF: Homogeneous time-resolved fluorescence IBMX: 3-isobutyl-1-methylxanthine Iva: 2-amino-2-methylbutyric acid iVal: 3-methylbutanoyl (isovalerianoyl) MRT: Average residence time Mtt: 4-methyl-trityl NMeR: N-methyl-L-arginine NMeQ: N-methyl-L-glutamine NMeY: N-methyl-L-tyrosine NMP: 1-methyl-pyrrolidin-2-one Oxyma: 2-cyano-2-(hydroxyimino)acetic acid ethyl ester 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: Trityl TRX: tranexamic acid, trans-4-(aminomethyl)cyclohexane-1-carboxylic acid TES: Triethylsilane TFA: Trifluoroacetic acid

[0066] The following compounds were synthesized. All compounds were obtained as TFA salts: compound 2 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGIELRHFLNHLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 328) MW (calculated): 6869.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.8 minutes; m / 3: m / 4:1718.1 m / 5: Compound 3 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGQRSYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 329) MW (calculated): 7106.0 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7 points;m / 3:2370.2 m / 4:1777.9 m / 5: Compound 4 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-Aib-RHY-Aib-NR-Aib-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 330) MW (calculated): 6736.5Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.0 minutes; m / 3: m / 4:1684.9 m / 5:

[0067] Compound 5 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-DLeu-R-DHis-YYNWLT-DArg-QR-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 331) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.8 minutes; m / 3: m / 4:1726.0 m / 5: Compound 6 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGQRYYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 332) MW (calculated): 7182.1 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:8.0 min;m / 3:2395.5 m / 4:1797.0 m / 5: Compound 7 Y-Aib-EGTFTSDYSI-Aib-LEEEAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys-eLys(1,2)(array number: 333) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.9 minutes; m / 3: m / 4:1725.9 m / 5: Compound 8 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVQWLIK(1,3)-GGPSSGQSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 334) MW (calculated): 6957.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.5min;m / 3:2320.3 m / 4:1740.7 m / 5:

[0068] Compound 9 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSYVSIRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 335) MW (calculated): 7034.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7min;m / 3:2346.7 m / 4:1760.1 m / 5: Compound 10 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPES-Aib-RHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eK (array number: 336) MW (calculated): 6970.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.1 points;m / 3:2324.9 m / 4:1743.9 m / 5: Compound 11 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(Allocation number: 337) MW (calculated): 6724.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2242.2 m / 4:1681.8 m / 5: Compound 12 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (Allocation number: 338) MW (calculated): 6696.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2232.7 m / 4:1674.9 m / 5:

[0069] Compound 13 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-Aib-RHYYNR-Aib-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 339) MW (calculated): 6814.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:33.6 minutes; m / 3: m / 4:1704.5 m / 5: Compound 14 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPRYYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 340) MW (calculated): 7151.1 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2385.6 m / 4:1789.2 m / 5: Compound 15 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 341) MW (calculated): 7033.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.6 points;m / 3:2346.2 m / 4:1759.9 m / 5: Compound 16 Y-Aib-EGTFTSDYSI-Aib-LE-Aib-EAQ-Aib-KFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 342) MW (calculated): 6915.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:38.2 minutes; m / 3: m / 4:1729.7 m / 5:

[0070] Compound 17 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYLNL-Aib-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 343) MW (calculated): 6749.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.1 minutes; m / 3: m / 4:1688.1 m / 5: Compound 18 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHY-Aib-NR-Aib-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 344) MW (calculated): 6764.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.3 minutes; m / 3: m / 4:1691.9 m / 5: Compound 19 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSYYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 345) MW (calculated): 7110.0 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.6 points;m / 3:2370.9 m / 4:1778.2 m / 5: Compound 20 Y-Aib-EGTFTSDYSI-Aib-LAAAAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 346) MW (calculated): 6728.5Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:39.8 minutes; m / 3: m / 4:1682.9 m / 5:

[0071] Compound 21 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLR-DHis-YYNWLT-DArg-QR-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 347) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.0 minutes; m / 3: m / 4:1725.9 m / 5: Compound 22 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGQSSYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(colocation number: 348) MW (calculated): 7036.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2347.4 m / 4:1760.7 m / 5: Compound 23 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEYYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 349) MW (calculated): 6994.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2331.8 m / 4:1749.4 m / 5: Compound 24 Y-Aib-EGTFTSDYSI-Aib-LE-Aib-KAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 350) MW (calculated): 6915.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.6 minutes; m / 3: m / 4:1723.2 m / 5:

[0072] Compound 25 Y-Aib-EGTFTSDYSI-Aib-LEAAKQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 351) MW (calculated): 6843.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:37.2 minutes; m / 3: m / 4:1711.7 m / 5: Compound 26 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-Aib-RHYYNWLT-hArg-QR-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 352) MW (calculated): 6886.7Da Synthesis and purification methods: S01; P01 LCMS:A01-B;Rt:34.3min;m / 3: m / 4:1722.4 m / 5: compound 27 [ka] The structure is disclosed in SEQ ID NO:353. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGVSIRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 353) MW (calculated): 6928.8Da Synthesis and purification methods: S02; P03 LCMS:A02-A;Rt:7.3 min;m / 3:2311.6 m / 4:1733.8 m / 5: compound 28 [ka] The structure is disclosed in SEQ ID NO:354. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO: 354) MW (calculated): 6829.6Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.3 minutes;m / 3: m / 4:1708.0 m / 5:

[0073] Compound 29 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 355) MW (calculated): 6684.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7min;m / 3:2228.8 m / 4:1672.0 m / 5: Compound 30 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 356) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.2 minutes; m / 3: m / 4:1725.9 m / 5: Compound 31 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVEWLIK(1,3)-GGPSSGQSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 357) MW (calculated): 6958.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.6 points;m / 3:2320.8 m / 4:1740.7 m / 5: Compound 32 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(Allocation number: 358) MW (calculated): 6974.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7 points;m / 3:2325.7 m / 4:1744.4 m / 5:

[0074] Compound 33 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSAVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 359) MW (calculated): 6942.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.5min;m / 3:2316.3 m / 4:1737.1 m / 5: Compound 34 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 360) MW (calculated): 6771.6 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.4 minutes; m / 3: m / 4:1693.6 m / 5: Compound 35 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGESLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eK (array number: 361) MW (calculated): 6957.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.2 points;m / 3:2320.5 m / 4:1740.4 m / 5: Compound 36 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 362) MW (calculated): 6990.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.6 points;m / 3:2331.2 m / 4:1748.3 m / 5:

[0075] Compound 37 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 363) MW (calculated): 6941.8 Da Synthesis method and refining method: S01; L20 LCMS:A01-A;Rt:7.2 minutes;m / 3:2314.9 m / 4:1736.3 m / 5: Compound 38 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGVS-Aib-RHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 364) MW (calculated): 6900.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.1 points;m / 3:2301.4 m / 4:1726.2 m / 5: Compound 39 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-Aib-RHYYNWLTRQ-NMeR-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 365) MW (calculated): 6886.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.4 minutes; m / 3: m / 4:1722.3 m / 5: Compound 40 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 366) MW (calculated): 7034.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.5min;m / 3:2345.5 m / 4:1759.4 m / 5:

[0076] Compound 41 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPQSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 367) MW (calculated): 6997.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.4 minutes;m / 3:2333.6 m / 4:1750.6 m / 5: Compound 42 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEYVSIRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 368) MW (calculated): 7076.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7min;m / 3:2360.0 m / 4:1770.6 m / 5: Compound 43 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 369) MW (calculated): 7086.9 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.3 minutes;m / 3: m / 4:1772.6 m / 5: Compound 44 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGQS-Aib-RHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 370) MW (calculated): 6929.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.0 points;m / 3:2311.2 m / 4:1733.2 m / 5:

[0077] Compound 45 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-eLys(1,2)(Allocation number: 371) MW (calculated): 6916.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.2 minutes; m / 3: m / 4:1729.8 m / 5: Compound 46 Y-Aib-EGTFTSDYSI-Aib-LEKEAQ-Aib-KFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 372) MW (calculated): 6958.8Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.6 minutes; m / 3: m / 4:1740.5 m / 5: Compound 47 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 373) MW (calculated): 6927.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.7 minutes;m / 3:2310.9 m / 4:1733.2 m / 5: Compound 48 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEPQSIRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 374) MW (calculated): 7039.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.1 points;m / 3:2347.9 m / 4:1761.1 m / 5:

[0078] Compound 49 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGES-Aib-RHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 375) MW (calculated): 6930.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.1 points;m / 3:2311.3 m / 4:1733.7 m / 5: Compound 50 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSYESLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (Allocation number: 376) MW (calculated): 7064.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 minutes;m / 3:2356.2 m / 4:1767.5 m / 5: Compound 51 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 377) MW (calculated): 6872.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:5.7min;m / 3:2291.8 m / 4:1719.6 m / 5: Compound 52 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-EEEE-OEG-OEG(1,2)(array number: 378) MW (calculated): 6817.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.3 minutes;m / 3:2273.8 m / 4:1705.5 m / 5:

[0079] Compound 53 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 379) MW (calculated): 6656.4 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.9 points;m / 3:2219.5 m / 4:1664.9 m / 5: Compound 54 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 380) MW (calculated): 6696.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:5.9 points;m / 3:2232.8 m / 4:1675.3 m / 5: Compound 55 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(Allocation number: 381) MW (calculated): 6946.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2316.4 m / 4:1737.6 m / 5: Compound 56 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 382) MW (calculated): 6874.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2292.4 m / 4:1719.8 m / 5:

[0080] Compound 57 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 383) MW (calculated): 6899.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2300.8 m / 4:1725.9 m / 5: Compound 58 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 384) MW (calculated): 6817.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.0 points;m / 3:2273.4 m / 4:1705.5 m / 5: Compound 59 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSYYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 385) MW (calculated): 6952.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt: min;m / 3:2318.5 m / 4:1738.9 m / 5: Compound 60 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 386) MW (calculated): 6784.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.2 points;m / 3:2262.5 m / 4:1697.3 m / 5:

[0081] Compound 61 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 387) MW (calculated): 6812.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2271.8 m / 4:1704.2 m / 5: Compound 62 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPRYYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 388) MW (calculated): 7152.1Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.2 minutes; m / 3: m / 4:1788.8 m / 5: Compound 63 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-EEEEE-eLys(1,2) (each with allocation numbers 389 and び635) MW (calculated): 6784.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.6 points;m / 3:2262.4 m / 4:1697.1 m / 5: Compound 64 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPESPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(Allocation number: 390) MW (calculated): 6858.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2286.9 m / 4:1715.2 m / 5:

[0082] Compound 65 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGGSEYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 391) MW (calculated): 6908.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2345.9 m / 4:1760.1 m / 5: Compound 66 Y-Aib-EGTFTSDYSI-Aib-LEEEAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 392) MW (calculated): 6902.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:14.1 minutes;m / 3: m / 4:1726.5 m / 5: Compound 67 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 393) MW (calculated): 6894.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2298.9 m / 4:1724.2 m / 5: Compound 68 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNR-Aib-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 394) MW (calculated): 6842.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.3 minutes; m / 3: m / 4:1711.4 m / 5:

[0083] Compound 69 Y-Aib-EGTFTSDYSI-Aib-LEKEKQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 395) MW (calculated): 6958.8Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:33.8 minutes; m / 3: m / 4:1740.4 m / 5: Compound 70 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPESPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 396) MW (calculated): 6853.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 minutes;m / 3:2284.9 m / 4:1714.4 m / 5: Compound 71 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLT-hArg-QR-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 397) MW (calculated): 6914.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.7 minutes; m / 3: m / 4:1729.4 m / 5: Compound 72 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGADLRHYLNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 398) MW (calculated): 6878.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.2 minutes; m / 3: m / 4:1720.4 m / 5:

[0084] Compound 73 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPESLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 399) MW (calculated): 6998.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.3min;m / 3:2334.1 m / 4:1751.0 m / 5: Compound 74 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-Aib-RHYYNWLTRQR-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 400) MW (calculated): 6872.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:34.3 minutes; m / 3: m / 4:1718.8 m / 5: Compound 75 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSYYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 401) MW (calculated): 6981.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.6 points;m / 3:2328.1 m / 4:1746.1 m / 5: Compound 76 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-Aib-RHY-Aib-NWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 402) MW (calculated): 6794.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.9 minutes; m / 3: m / 4:1699.4 m / 5:

[0085] Compound 77 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 403) MW (calculated): 6927.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2310.2 m / 4:1733.1 m / 5: Compound 78 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 404) MW (calculated): 7076.0 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2358.9 m / 4:1769.7 m / 5: Compound 79 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNL-Aib-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 405) MW (calculated): 6799.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.9 minutes; m / 3: m / 4:1700.6 m / 5: Compound 80 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSYYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 406) MW (calculated): 7111.0 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.7 points;m / 3:2370.9 m / 4:1778.5 m / 5:

[0086] Compound 81 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 407) MW (calculated): 6747.5 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.1 points;m / 3:2250.8 m / 4:1688.3 m / 5: Compound 82 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPESPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(Allocation number: 408) MW (calculated): 6886.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:11.4 points;m / 3:2296.2 m / 4:1722.4 m / 5: Compound 83

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[0087] compound 85 [ka] The structure is disclosed in SEQ ID NO:411. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTR-NMeQ-RY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 411) MW (calculated): 6914.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.7 minutes;m / 3: m / 4: m / 5:1383.8 Compound 86 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYLNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 412) MW (calculated): 6850.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.9 minutes; m / 3: m / 4:1713.5 m / 5: Compound 87 Y-Aib-DGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 413) MW (calculated): 6886.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:35.4 minutes; m / 3: m / 4:1722.4 m / 5: Compound 88 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 414) MW (calculated): 7087.9 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.4 minutes;m / 3: m / 4:1772.7 m / 5:

[0088] Compound 89 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 415) MW (calculated): 6983.8Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.6 minutes;m / 3:2328.9 m / 4:1746.9 m / 5: Compound 90 Y-Aib-EGTFTSDYSI-Aib-LEDQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 416) MW (calculated): 6887.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.3 minutes; m / 3: m / 4:1722.7 m / 5: Compound 91 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGATLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 417) MW (calculated): 6914.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2306.6 m / 4:1730.1 m / 5: Compound 92 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 418) MW (calculated): 7028.9Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3min;m / 3:2343.6 m / 4:1758.1 m / 5:

[0089] Compound 93 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEYESLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 419) MW (calculated): 7106.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.8 points;m / 3:2370.5 m / 4:1777.8 m / 5: Compound 94 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGISLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 420) MW (calculated): 6942.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:11.1 points;m / 3:2315.9 m / 4:1737.1 m / 5: Compound 95 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 421) MW (calculated): 6940.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.8 minutes; m / 3: m / 4:1735.9 m / 5: Compound 96 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 422) MW (calculated): 6928.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 minutes;m / 3:2310.1 m / 4:1732.7 m / 5:

[0090] Compound 97 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 423) MW (calculated): 6643.4 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.9 minutes; m / 3: m / 4:1661.5 m / 5: Compound 98 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSAASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 424) MW (calculated): 6914.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:11.0 points;m / 3:2306.3 m / 4:1730.1 m / 5: Compound 99 Y-Aib-EGTFTSDYSI-Aib-LEGQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 425) MW (calculated): 6829.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.8 minutes; m / 3: m / 4:1708.1 m / 5: Compound 100 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG-eLys(1,2)(array number: 426) MW (calculated): 6933.8 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.5 minutes; m / 3: m / 4:1734.0 m / 5:

[0091] Compound 101 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 427) MW (calculated): 6981.8 Da Synthesis method and refining method: S01; L20 LCMS:A01-B; Rt:7.4 minutes; m / 3:2328.2 m / 4:1746.3 m / 5: Compound 102 Y-Aib-EGTFTSDYSI-Aib-LEAQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 428) MW (calculated): 6843.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:37.5 minutes; m / 3: m / 4: m / 5:1369.4 Compound 103 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-Tle-RHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 429) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:34.9 minutes; m / 3: m / 4: m / 5:1380.9 Compound 104 Y-Aib-EGTFTSDYSILLEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 430) MW (calculated): 6928.8Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.4 minutes; m / 3: m / 4:1732.9 m / 5:

[0092] Compound 105 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys-eLys(1,2)(Allocation number: 431) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.9 minutes; m / 3: m / 4:1725.9 m / 5: Compound 106 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYINWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 432) MW (calculated): 6850.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:35.9 minutes; m / 3: m / 4: m / 5:1370.8 Compound 107 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 433) MW (calculated): 6942.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.7 minutes; m / 3: m / 4:1736.4 m / 5: Compound 108 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 434) MW (calculated): 6854.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.9 minutes;m / 3: m / 4:1714.4 m / 5:

[0093] Compound 109 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLLK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 435) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:35.2 minutes; m / 3: m / 4:1725.9 m / 5: Compound 110 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-eLys(1,2)(array number: 436) MW (calculated): 6917.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.5 minutes; m / 3: m / 4:1730.1 m / 5: Compound 111 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 437) MW (calculated): 7014.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.8 points;m / 3:2339.5 m / 4:1754.9 m / 5: Compound 112 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 438) MW (calculated): 6932.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2312.2 m / 4:1734.1 m / 5:

[0094] Compound 113 Y-Aib-EGTFTSDLSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 439) MW (calculated): 6891.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.7 minutes;m / 3: m / 4:1723.7 m / 5: Compound 114 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 440) MW (calculated): 6969.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 minutes;m / 3:2323.6 m / 4:1743.1 m / 5: Compound 115 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRYYNWLTR-NMeQ-RY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 441) MW (calculated): 6955.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.8 minutes;m / 3: m / 4:1739.6 m / 5: Compound 116 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 442) MW (calculated): 6901.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.7 minutes; m / 3: m / 4:1726.2 m / 5:

[0095] Compound 117 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASVRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 443) MW (calculated): 6886.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2297.3 m / 4:1722.9 m / 5: Compound 118 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGAS-AiB;RHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 444) MW (calculated): 6872.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.5 minutes; m / 3: m / 4:1718.9 m / 5: Compound 119 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLR-Tle-YYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 445) MW (calculated): 6876.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.0 minutes; m / 3: m / 4: m / 5:1376.1 Compound 120 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 446) MW (calculated): 6973.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.9 points;m / 3:2325.1 m / 4:1744.6 m / 5:

[0096] Compound 121 Y-Aib-EGTFTSDYSI-Aib-LESQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 447) MW (calculated): 6859.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:39.8 minutes; m / 3: m / 4:1715.6 m / 5: Compound 122 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEPESLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 448) MW (calculated): 7040.9Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.3 points;m / 3:2347.9 m / 4:1761.4 m / 5: Compound 123 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGQSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 449) MW (calculated): 6931.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.9 points;m / 3:2312.0 m / 4:1732.4 m / 5: Compound 124 Y-Aib-EGTFTSDYSI-Aib-LEQQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 450) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.0 minutes; m / 3: m / 4: m / 5:1381.0

[0097] Compound 125 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRYYNWLTRQ-NMeR-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 451) MW (calculated): 6955.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.5 minutes; m / 3: m / 4:1739.8 m / 5: Compound 126 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 452) MW (calculated): 7006.9Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.7 minutes; m / 3: m / 4:1752.5 m / 5: Compound 127 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGESLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 453) MW (calculated): 6958.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 minutes;m / 3:2320.8 m / 4:1740.8 m / 5: Compound 128 Y-Aib-EGTFTSDYSI-Aib-LDKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 454) MW (calculated): 6886.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.9 minutes; m / 3: m / 4:1722.3 m / 5:

[0098] Compound 129 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASL-Aib-HYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 455) MW (calculated): 6829.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.0 minutes; m / 3: m / 4:1708.2 m / 5: Compound 130 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFIEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 456) MW (calculated): 6914.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.4 minutes; m / 3: m / 4:1729.3 m / 5: Compound 131 Y-Aib-EGTFTSDYSI-Aib-LERQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 457) MW (calculated): 6928.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:35.4 points; m / 3: m / 4: m / 5:1386.5 Compound 132 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASIRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 458) MW (calculated): 6900.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A; Rt:7.3 minutes;m / 3:2301.5 m / 4:1726.6 m / 5:

[0099] Compound 133 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHY-Tle-NWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 459) MW (calculated): 6851.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.0 minutes; m / 3: m / 4:1713.4 m / 5: Compound 134 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGQSIRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 460) MW (calculated): 6999.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2334.4 m / 4:1750.9 m / 5: Compound 135 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEYLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 461) MW (calculated): 6877.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.2 minutes; m / 3: m / 4:1720.1 m / 5: Compound 136 Y-Aib-EGTFTSDYSI-Aib-LEKAAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 462) MW (calculated): 6843.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.1 minutes; m / 3: m / 4:1711.7 m / 5:

[0100] Compound 137 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNW-Tle-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 463) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.4 minutes; m / 3: m / 4:1725.9 m / 5: Compound 138 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 464) MW (calculated): 6785.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.0 points;m / 3:2262.8 m / 4:1697.6 m / 5: Compound 139 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(array number: 465) MW (calculated): 6856.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A; Rt:7.1 points;m / 3:2286.8 m / 4:1713.0 m / 5: Compound 140 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(Allocation number: 466) MW (calculated): 6945.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 points;m / 3:2316.6 m / 4:1737.6 m / 5:

[0101] Compound 141 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 467) MW (calculated): 6714.5Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.8 points;m / 3:2239.3 m / 4:1679.7 m / 5: Compound 142 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 468) MW (calculated): 6986.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.0 points;m / 3:2329.8 m / 4:1747.6 m / 5: Compound 143 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 469) MW (calculated): 6826.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.8 points;m / 3:2276.4 m / 4:1707.7 m / 5: Compound 144 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(Allocation number: 470) MW (calculated): 6730.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.2 minutes;m / 3:2244.5 m / 4:1683.6 m / 5:

[0102] Compound 145 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 471) MW (calculated): 6834.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.8 points;m / 3:2279.3 m / 4:1709.6 m / 5: Compound 146 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 472) MW (calculated): 6859.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.0 points;m / 3:2287.7 m / 4:1716.0 m / 5: Compound 147 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 473) MW (calculated): 6743.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2248.8 m / 4:1686.9 m / 5: Compound 148 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 474) MW (calculated): 6824.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.8 points;m / 3:2275.9 m / 4:1707.1 m / 5:

[0103] Compound 149 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 475) MW (calculated): 6955.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.2 points;m / 3:2319.9 m / 4:1740.0 m / 5: Compound 150 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 476) MW (calculated): 6777.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.2 points;m / 3:2260.5 m / 4:1695.4 m / 5: Compound 151 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(colocation number: 477) MW (calculated): 6843.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.9 points;m / 3:2281.9 m / 4:1711.8 m / 5: Compound 152 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 478) MW (calculated): 6785.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.9 points;m / 3:2263.3 m / 4:1697.4 m / 5:

[0104] Compound 153 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 479) MW (calculated): 6971.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:7.5min;m / 3:2325.0 m / 4:1743.9 m / 5: Compound 154 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 480) MW (calculated): 6842.7Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:8.9 points;m / 3:2282.1 m / 4:1711.6 m / 5: Compound 155 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-EEEEE-eLys(1,2)(each allocated number 481 and び635) MW (calculated): 6826.7Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.6 points;m / 3:2276.8 m / 4:1707.6 m / 5: Compound 156 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 482) MW (calculated): 6818.6Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 minutes;m / 3:2273.6 m / 4:1705.4 m / 5:

[0105] Compound 157 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-EEE-OEG-OEG(1,2)(array number: 483) MW (calculated): 6688.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2249.8 m / 4:1687.8 m / 5:6746.5 Compound 158 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 484) MW (calculated): 6816.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2273.2 m / 4:1705.2 m / 5: Compound 159 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 485) MW (calculated): 6801.6Da Synthesis method and purification method: S02; P03 LCMS:A02-A; Rt:6.6 points;m / 3:2268.2 m / 4:1701.4 m / 5: Compound 160 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 486) MW (calculated): 6746.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.8 points;m / 3:2249.8 m / 4:1687.6 m / 5:

[0106] Compound 161 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPEEPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 487) MW (calculated): 6900.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2301.2 m / 4:1726.2 m / 5: Compound 162 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(array number: 488) MW (calculated): 6811.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:8.8 points;m / 3:2271.5 m / 4:1704.1 m / 5: Compound 163 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 489) MW (calculated): 6818.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2273.8 m / 4:1705.6 m / 5: Compound 164 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(Allocation number: 490) MW (calculated): 6956.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:8.2 points;m / 3:2319.5 m / 4:1740.3 m / 5:

[0107] Compound 165 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 491) MW (calculated): 6885.8Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.8 minutes;m / 3:2295.9 m / 4:1722.1 m / 5: Compound 166 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPESGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 492) MW (calculated): 6689.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.2 points;m / 3:2231.0 m / 4:1673.6 m / 5: Compound 167 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 493) MW (calculated): 6904.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 min;m / 3:2302.7 m / 4:1727.3 m / 5: Compound 168 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPRSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 494) MW (calculated): 6969.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.9 points;m / 3:2324.9 m / 4:1743.5 m / 5:

[0108] Compound 169 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 495) MW (calculated): 6853.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2285.1 m / 4:1714.0 m / 5: Compound 170 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 496) MW (calculated): 6871.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.7 points;m / 3:2291.8 m / 4:1719.1 m / 5: Compound 171 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 497) MW (calculated): 6705.5Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.1 minutes;m / 3:2236.5 m / 4:1677.6 m / 5: Compound 172 Y-Aib-EGTFTSDLSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 498) MW (calculated): 6850.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.4 minutes; m / 3: m / 4:1713.4 m / 5:

[0109] Compound 173 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 499) MW (calculated): 6857.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.0 points;m / 3:2286.9 m / 4:1715.5 m / 5: Compound 174 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 500) MW (calculated): 6656.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:5.9 points;m / 3:2220.1 m / 4:1665.7 m / 5: Compound 175 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 501) MW (calculated): 6844.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:8.0 points;m / 3:2282.2 m / 4:1712.2 m / 5: Compound 176 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-EEEEE(1,2)(each allocated number is 502 and び636) MW (calculated): 6714.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2239.9 m / 4:1679.8 m / 5:

[0110] Compound 177 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-EEEE-OEG-OEG(1,2)(each arrangement number is 503 and び634) MW (calculated): 6859.7Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.3 minutes;m / 3:2287.1 m / 4:1716.0 m / 5: Compound 178 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(Allocation number: 504) MW (calculated): 6683.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7min;m / 3:2228.3 m / 4:1671.5 m / 5: Compound 179 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-EEEEEE(1,2)(each with serial numbers 505 and び637) MW (calculated): 6843.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.0 points;m / 3:2282.2 m / 4:1711.8 m / 5: Compound 180 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(Allocation number: 506) MW (calculated): 6655.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2218.6 m / 4:1664.3 m / 5:

[0111] Compound 181 Y-Aib-EGTFTSDYSI-Aib-LEEQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 507) MW (calculated): 6772.6 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:36.8 minutes; m / 3: m / 4:1693.8 m / 5: Compound 182 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLR-Aib-YYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 508) MW (calculated): 6848.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.1 minutes; m / 3: m / 4:1712.9 m / 5: Compound 183 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 509) MW (calculated): 6877.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2293.2 m / 4:1720.3 m / 5: Compound 184 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHY-Aib-NWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 510) MW (calculated): 6822.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.2 minutes; m / 3: m / 4:1706.5 m / 5:

[0112] Compound 185 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(colocation number: 511) MW (calculated): 6871.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.3 minutes;m / 3: m / 4:1718.7 m / 5: Compound 186 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRYYNWLTR-bHGln-RY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 512) MW (calculated): 6955.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.0 minutes; m / 3: m / 4:1739.6 m / 5: Compound 187 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 513) MW (calculated): 6930.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:8.6 points;m / 3:2311.2 m / 4:1733.4 m / 5: Compound 188 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-EEE-OEG-OEG(1,2)(array number: 514) MW (calculated): 6730.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.5 minutes;m / 3:2243.9 m / 4:1683.6 m / 5:

[0113] Compound 189 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 515) MW (calculated): 6918.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 minutes;m / 3:2306.7 m / 4:1730.5 m / 5: Compound 190 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNW-DArg-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 516) MW (calculated): 6943.8 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:34.1 minutes; m / 3: m / 4:1736.6 m / 5: Compound 191 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQR-Tle-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 517) MW (calculated): 6850.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.4 minutes; m / 3: m / 4:1713.4 m / 5: Compound 192 Y-Aib-EGTFTSDYSI-Aib-LE-KAc-QAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 518) MW (calculated): 6942.8 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:37.0 minutes; m / 3: m / 4:1736.3 m / 5:

[0114] Compound 193 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 519) MW (calculated): 6887.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.6 points;m / 3:2297.1 m / 4:1723.5 m / 5: Compound 194 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 520) MW (calculated): 6613.4 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7 points;m / 3:2205.7 m / 4:1654.4 m / 5: Compound 195 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNLLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 521) MW (calculated): 6827.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.0 minutes; m / 3: m / 4:1707.7 m / 5: Compound 196 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-EEEEEE-eLys(1,2) (each allocated number 522 and び643) MW (calculated): 6955.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.4 points;m / 3:2319.1 m / 4:1739.8 m / 5:

[0115] Compound 197 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGALLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 523) MW (calculated): 6927.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.7 minutes; m / 3: m / 4:1732.4 m / 5: Compound 198 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 524) MW (calculated): 6830.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.4 minutes;m / 3: m / 4:1708.3 m / 5: Compound 199 Y-Aib-EGTFTSDYSI-Aib-LE-Aib-QAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 525) MW (calculated): 6857.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:38.5 minutes; m / 3: m / 4:1715.2 m / 5: Compound 200 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 526) MW (calculated): 6813.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.5 minutes;m / 3:2272.0 m / 4:1704.7 m / 5:

[0116] Compound 201 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 527) MW (calculated): 6963.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.9 points;m / 3:2322.1 m / 4:1742.1 m / 5: Compound 202 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 528) MW (calculated): 6585.4 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.9 points;m / 3:2196.5 m / 4:1647.5 m / 5: Compound 203 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSYYASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 529) MW (calculated): 6953.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.5min;m / 3:2318.6 m / 4:1739.0 m / 5: Compound 204 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNW-DAsp-TRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 530) MW (calculated): 6902.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:34.6 minutes; m / 3: m / 4:1726.4 m / 5:

[0117] Compound 205 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 531) MW (calculated): 6862.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2288.4 m / 4:1716.7 m / 5: Compound 206 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPEEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 532) MW (calculated): 6928.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.9 points;m / 3:2310.6 m / 4:1733.1 m / 5: Compound 207 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 533) MW (calculated): 7128.9 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.4 minutes;m / 3: m / 4:1783.0 m / 5: Compound 208 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTR-bHGln-RY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 534) MW (calculated): 6914.8 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:35.1 minutes; m / 3: m / 4:1729.5 m / 5:

[0118] Compound 209 Y-Aib-EGTFTSDYSI-Aib-LELQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 535) MW (calculated): 6885.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:39.6 minutes; m / 3: m / 4:1722.1 m / 5: Compound 210 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLLHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 536) MW (calculated): 6857.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:37.1 minutes; m / 3: m / 4:1715.2 m / 5: Compound 211 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-DAsp-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 537) MW (calculated): 6930.7 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:35.1 minutes; m / 3: m / 4:1733.4 m / 5: Compound 212 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 538) MW (calculated): 6800.6Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:11.7 minutes;m / 3:2268.3 m / 4:1701.3 m / 5:

[0119] Compound 213 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYY-Aib-WLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 539) MW (calculated): 6871.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.5 minutes; m / 3: m / 4:1718.6 m / 5: Compound 214 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQR-DTyr-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 540) MW (calculated): 6900.7Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.8 minutes; m / 3: m / 4:1725.8 m / 5: Compound 215 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 541) MW (calculated): 6958.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.1 points;m / 3:2320.6 m / 4:1740.7 m / 5: Compound 216 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-DArg-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 542) MW (calculated): 6971.8 Da Synthesis method and purification method: S01; P01 LCMS:A01-B; Rt:34.0 minutes; m / 3: m / 4:1743.7 m / 5:

[0120] Compound 217 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEYVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 543) MW (calculated): 7076.9 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.5min;m / 3:2359.6 m / 4:1769.8 m / 5: Compound 218 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYN-Aib-LTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 544) MW (calculated): 6799.6 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.0 minutes; m / 3: m / 4:1700.6 m / 5: Compound 219 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 545) MW (calculated): 6846.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:11.7 minutes;m / 3:2283.3 m / 4:1712.5 m / 5: Compound 220

change

[0121] compound 221 [ka] The structure is disclosed in SEQ ID NO:547. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 547) MW (calculated): 6900.7Da Synthesis and purification methods: S01; P02 LCMS:A01-A;Rt:12.8 min;m / 3: m / 4:1725.9 m / 5 compound 222 [ka] The structure is disclosed in SEQ ID NO:548. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTR-NMeQ-RY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 548) MW (calculated): 6956.8Da Synthesis and purification methods: S01; P02 LCMS:A01-A;Rt:12.7min;m / 3: m / 4:1740.0 m / 5: compound 223 [ka] The structure is disclosed in SEQ ID NO:549. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO: 549) MW (calculated): 6813.6Da Synthesis and purification methods: S01; L20 LCMS:A01-A;Rt:6.7 min;m / 3:2272.1 m / 4:1704.5 m / 5: compound 224 [ka] The structure is disclosed in SEQ ID NO:550. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 550) MW (calculated): 7070.9Da Synthesis method and purification method: S01; P02 LCMS: A01 - B; Rt: 34.4 minutes; m / z: m / 4: m / 5: 1415.0

[0122] Compound 225

Chem.

[0123] Compound 229 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 555) MW (calculated): 6933.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2312.1 m / 4:1734.4 m / 5: Compound 230 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 556) MW (calculated): 6855.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.0 minutes;m / 3: m / 4:1714.6 m / 5: Compound 231 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFIEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 557) MW (calculated): 6860.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.7 minutes;m / 3: m / 4:1716.0 m / 5: Compound 232 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSYGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 558) MW (calculated): 6976.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2326.8 m / 4:1745.9 m / 5:

[0124] Compound 233 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 559) MW (calculated): 6982.8Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:34.6 minutes; m / 3: m / 4:1746.4 m / 5: Compound 234 Y-Aib-EGTFTSDLSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 560) MW (calculated): 6892.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:36.4 minutes; m / 3: m / 4:1723.9 m / 5: Compound 235 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 561) MW (calculated): 6772.6 Da Synthesis method and refining method: S01; L20 LCMS:A01-A;Rt:6.7 points;m / 3:2259.1 m / 4:1694.4 m / 5: Compound 236 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRYYNWLTRQ-NMeR-Y-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 562) MW (calculated): 6956.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.7 minutes; m / 3: m / 4:1739.9 m / 5:

[0125] Compound 237 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGESLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 563) MW (calculated): 7000.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.2 points;m / 3:2334.9 m / 4:1751.3 m / 5: Compound 238 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 564) MW (calculated): 6643.4 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.7 minutes;m / 3: m / 4:1661.6 m / 5: Compound 239 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-EEEE-OEG-OEG(1,2)(each arrangement number is 565 and び638) MW (calculated): 6845.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.9 points;m / 3:2283.0 m / 4:1712.3 m / 5: Compound 240 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-EEEEE-eLys(1,2)(each allocation number is 566 and び639) MW (calculated): 6812.7Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.5 minutes;m / 3:2272.1 m / 4:1704.2 m / 5:

[0126] Compound 241 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGVSLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 567) MW (calculated): 6970.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3min;m / 3:2323.8 m / 4:1743.4 m / 5: Compound 242 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 568) MW (calculated): 6812.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.6 minutes;m / 3:2272.0 m / 4:1704.2 m / 5: Compound 243 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 569) MW (calculated): 6684.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2228.7 m / 4:1672.1 m / 5: Compound 244 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSTGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 570) MW (calculated): 6914.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.8 minutes;m / 3:2306.2 m / 4:1729.9 m / 5:

[0127] Compound 245 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(Allocation number: 571) MW (calculated): 6898.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:8.6 points;m / 3:2300.5 m / 4:1725.9 m / 5: Compound 246 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(Allocation number: 572) MW (calculated): 6946.8 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.0 points;m / 3:2316.7 m / 4:1737.6 m / 5: Compound 247 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFIEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 573) MW (calculated): 6542.3 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.7 minutes;m / 3: m / 4:1636.4 m / 5: Compound 248 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 574) MW (calculated): 6731.5Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3min;m / 3:2245.0 m / 4:1684.0 m / 5:

[0128] Compound 249 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-EEEEEE-eLys(1,2) (each with allocation numbers 575 and び643) MW (calculated): 6913.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.8 points;m / 3:2305.4 m / 4:1729.5 m / 5: Compound 250 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 576) MW (calculated): 6656.4 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.0 points;m / 3:2219.5 m / 4:1664.9 m / 5: Compound 251 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 577) MW (calculated): 6819.6 Da Synthesis method and refining method: S01; L20 LCMS:A01-A;Rt:6.2 points;m / 3:2274.4 m / 4:1705.9 m / 5: Compound 252 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(colocation number: 578) MW (calculated): 6785.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.8 points;m / 3:2263.0 m / 4:1697.4 m / 5:

[0129] Compound 253 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 579) MW (calculated): 6615.4 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.4 minutes;m / 3: m / 4:1654.7 m / 5: 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 method and purification method: S02; P03 LCMS: A02-A; Rt: 7.2 min; m / z: 2259.7 m / z4: 1695.0 m / z5: Compound 255

Chemical formula

[0130] 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) MW (calculated): 6656.4 Da Synthesis method and purification method: S02; P03 LCMS: A02-B; Rt: 10.4 min; m / z: 2220.0 m / z4: 1665.3 m / z5: 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 method and purification method: S01; P02 LCMS: A01-A; Rt: 12.5 min; m / z3: m / z4: 1708.9 m / z5: Compound 259

Chemical Structure

[0131] Compound 261 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSSGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 587) MW (calculated): 6905.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2303.4 m / 4:1727.7 m / 5: Compound 262 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 588) MW (calculated): 6529.3 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.9 minutes;m / 3: m / 4:1633.1 m / 5: Compound 263 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEPASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 589) MW (calculated): 6825.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:12.5 minutes;m / 3:2275.8 m / 4:1707.2 m / 5: Compound 264 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-EEEEEE(1,2)(each arrangement number is 590 and び637) MW (calculated): 6785.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.3 minutes;m / 3:2263.0 m / 4:1697.4 m / 5:

[0132] Compound 265

change

[0133] Compound 269 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 595) MW (calculated): 6845.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.7 points;m / 3:2282.5 m / 4:1712.3 m / 5: Compound 270 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVQWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 596) MW (calculated): 6817.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.1 minutes;m / 3:2273.8 m / 4:1705.2 m / 5: Compound 271 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 597) MW (calculated): 6614.4 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2205.7 m / 4:1654.6 m / 5: Compound 272 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 598) MW (calculated): 6570.3 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.4 points;m / 3:2191.6 m / 4:1644.1 m / 5:

[0134] Compound 273 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 599) MW (calculated): 6775.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.8 points;m / 3:2259.7 m / 4:1694.9 m / 5: Compound 274 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-OEG(1,2)(array number: 600) MW (calculated): 6602.4Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:8.9 points;m / 3:2201.8 m / 4:1651.7 m / 5: Compound 275 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 601) MW (calculated): 7000.8Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.3 minutes;m / 3:2335.4 m / 4:1751.1 m / 5: Compound 276 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 602) MW (calculated): 6586.3 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.1 points;m / 3:2196.1 m / 4:1647.5 m / 5:

[0135] Compound 277 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTR-bHGln-RY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 603) MW (calculated): 6956.8 Da Synthesis method and purification method: S01; P02 LCMS:A01-B; Rt:35.1 minutes; m / 3: m / 4:1740.0 m / 5: Compound 278 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 604) MW (calculated): 6847.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.8 minutes;m / 3: m / 4:1712.7 m / 5: Compound 279 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-EFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(array number: 605) MW (calculated): 6957.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:8.4 points;m / 3:2320.4 m / 4:1741.0 m / 5: Compound 280 Y-Aib-EGTFTSDYSI-Aib-LEKQAE-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 606) MW (calculated): 6557.3 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:14.1 minutes;m / 3: m / 4:1640.2 m / 5:

[0136] 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)(each SEQ ID No. 607 and 640) MW (calculated): 6527.3 Da Synthesis method and purification method: S02; P03 LCMS: A02-A; Rt: 7.3 min; m / z: 2177.4 m / z4: 1632.6 m / z5: 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 method and purification method: S02; P03 LCMS: A02-A; Rt: 7.5 min; m / z: 2163.1 m / z4: 1623.1 m / z5: 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 method and purification method: S01; P02 LCMS: A01-A; Rt: 14.0 min; m / z: m / z4: 1643.5 m / z5: Compound 284

Chemical Structure

[0137] compound 285 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPEEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 611) MW (calculated): 6984.8Da Synthesis and purification methods: S02; P03 LCMS:A02-B;Rt:10.7 min;m / 3:2329.3 m / 4:1747.2 m / 5: compound 286 [ka] The structure is disclosed in SEQ ID NO:612. Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2) (SEQ ID NO: 612) MW (calculated): 6942.8Da Synthesis and purification methods: S01; P02 LCMS:A01-A;Rt:12.7 minutes;m / 3:2315.4 m / 4:1736.7 m / 5: Compound 287 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-OEG-OEG(1,2)(array number: 613) MW (calculated): 6846.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.9 points;m / 3:2283.2 m / 4:1712.5 m / 5: Compound 288 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 614) MW (calculated): 7071.9 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:12.9 minutes;m / 3: m / 4:1768.6 m / 5:

[0138] Compound 289 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 615) MW (calculated): 6685.5Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.6 minutes;m / 3: m / 4:1672.2 m / 5: Compound 290 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 616) MW (calculated): 6813.7 Da Synthesis method and purification method: S01; P02 LCMS:A01-A;Rt:13.0 points;m / 3: m / 4: m / 5:1363.6 Compound 291 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-EEEE(1,2)(each arrangement number is 617 and び640) MW (calculated): 6657.4 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.6 minutes;m / 3:2117.4 m / 4:1633.3 m / 5: Compound 292 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 618) MW (calculated): 6657.4 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.6 points;m / 3:2220.6 m / 4:1665.5 m / 5:

[0139] Compound 293 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(Allocation number: 619) MW (calculated): 6914.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:6.8 points;m / 3:2306.3 m / 4:1729.9 m / 5: Compound 294 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu(1,2)(array number: 620) MW (calculated): 6528.3Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.5 minutes;m / 3:2177.2 m / 4:1633.1 m / 5: Compound 295 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-eLys(1,2)(array number: 621) MW (calculated): 6785.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:9.4 points;m / 3:2262.9 m / 4:1697.4 m / 5: 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 method and purification method: S02; P03 LCMS: A02-B; Rt: 10.1 min; m / z: 2263.2 m / z4: 1697.7 m / z5:

[0140] Compound 297

Chemical Structure

[0141] Compound 301 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(array number: 627) MW (calculated): 6798.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.4 minutes;m / 3:2267.1 m / 4:1700.9 m / 5: Compound 302 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-EEEEEE(1,2)(each arrangement number is 628 and び637) MW (calculated): 6786.5Da Synthesis method and purification method: S02; P03 LCMS:A02-B;Rt:10.5 minutes;m / 3:2263.1 m / 4:1697.6 m / 5: Compound 303 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(Allocation number: 629) MW (calculated): 6899.7 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 minutes;m / 3:2301.3 m / 4:1726.1 m / 5: Compound 304 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C18DA-gGlu-gGlu-gGlu-gGlu-gGlu-AHX(1,2)(array number: 630) MW (calculated): 6770.6 Da Synthesis method and purification method: S02; P03 LCMS:A02-A;Rt:7.2 points;m / 3:2258.0 m / 4:1694.0 m / 5:

[0142] Compound 305 Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK(1,3)-GGPSEGASLRHYYNWLTRQRY-NH2.C20DA-gGlu-gGlu-gGlu-gGlu-gGlu-gGlu(1,2) (SEQ ID NO: 631) MW (calculated): 6814.6Da Synthesis and purification methods: S01; P02 LCMS:A01-B;Rt:35.5 min;m / 3: m / 4: m / 5:1363.7 Literature 1 NMeY-Aib-EGT-aMeF-TSDK(1,3)-SI-Aib-LEKQRQ-Iva-EFVRHLLNK-Aib-TRQRY-NH2.C16A-GGGG(1,2) (SEQ ID NOs: 632 and 641, respectively) Example 41 of EP3467106 Solubility:<1mg / ml (pH7) Literature 2 NMeY-Aib-EGT-aMeF-TSDK(1,3)-SI-Aib-LEKQRQ-Iva-EFVRHLLNK-Aib-TRQRY-NH2.C18DA-GGGG(1,2) (SEQ ID NOs: 633 and 642, respectively) Example 42 of EP3467106 Solubility:<1mg / ml (pH7)

[0143] Example The following examples illustrate certain specific embodiments of the present invention. Except as otherwise specified, the following examples were carried out using standard techniques that are well known and routine to those skilled in the art.

[0144] Example 1: hGLP1R / hGIPR / hNPY2R CreLuc Assay in 0.5% and 100% Plasma CHO and HEK-293 recombinant cell lines express a luciferase reporter gene under the control of a cAMP response element (CRE). Secondary recombinant proteins, GLP-1 and NPY2 receptors, were expressed in reporter gene-expressing HEK cells, and GIP receptors in reporter gene-expressing CHO cells, respectively. Stimulation of these recombinant cells with agonists induces 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), inducing transcription of the luciferase reporter gene. Serially diluted peptides in 100% DMSO were transferred to a 384-well assay plate with 5 μl of pre-dispensed assay buffer (1x HBSS, 20 mM HEPES, pH 7.4, supplemented with 0.5% human plasma) using acoustic dispensing with a Labcyte ECHO. Cryopreserved transgenic reporter gene cells were thawed in assay buffer. 20 μl (10,000 cells / well) was added to the plate containing peptide and incubated for 4 hours at 37°C in a humidified incubator. After incubation, the assay plate was equilibrated to room temperature, and 25 μl of Bright-Glo™ luciferase reagent was added, incubated for 10 minutes at room temperature, and luminescence was analyzed (Envision Reader). Compound concentration-response evaluation was performed at eight concentrations of peptide (covering 4 decades). EC50 values ​​were calculated by nonlinear regression using a concentration-response sigmoidal curve with variable slope. The same assay was performed in the presence of 100% plasma without the addition of any additional buffer components.

[0145] The results are summarized in Table 3 below. [Table 9-1] [Table 9-2] [Table 9-3] [Table 9-4] [Table 9-5] [Table 9-6] [Table 9-7]

[0146] Example 2: Solubility The peptide (as TFA salt) was weighed onto a filter unit (Mini-UniPrep Syringeless Filter 0.45 μm, Whatman PVDF) and 0.1 M phosphate buffer, pH 7, was added to obtain a final peptide concentration of 10 mg / mL. The filter unit was shaken horizontally at 600 rpm for 2 hours at room temperature to dissolve the peptide. The sample was then filtered to remove any insoluble particles. Controls were prepared by weighing the corresponding peptide solid material and dissolving it in an appropriate medium (e.g., ACN:HO) to a final concentration of 1 mg / mL. Both the control and the sample were analyzed by reverse-phase chromatography. The peak area of ​​the sample was compared to that of the control, and the solubility was calculated based on the ratio. The pH was measured and recorded for each sample.

[0147] Example 3: Mouse PK Pharmacokinetic parameters of peptides were measured after intravenous administration to NMRI mice. Male NMRI mice weighing 30 to 40 g were obtained from Janvier Laboratories (France). Mice were housed in standard cages with a 12:12-h light / dark cycle and ad libitum access to standard food and water. Each test peptide was dissolved in 50 mM phosphate buffer (pH 7.4) / 3.5% mannitol. Intravenous administration of 30–60 nmol / kg was administered via the posterior vein. Blood samples were collected serially from conscious mice into EDTA-containing vials via the saphenous vein at various time points up to 56 h post-administration. Plasma was then prepared by centrifugation at approximately 5,000 rpm for 5 min and stored at -20°C until quantification of peptide plasma levels by liquid chromatography-mass spectrometry (LC-MS). Individual plasma concentration-time profiles were analyzed using a noncompartmental approach, and the resulting pharmacokinetic parameters were calculated. The mean residence time (MRT) of the GGY peptide of the present invention in mice was measured and is summarized in Table 4 below.

[0148] [Table 10]

[0149] Example 4: Effects of acute food intake in normal NMRI mice Three-week-old male NMRI mice were obtained from Janvier (Janvier Labs, France) or Charles River (Charles River Research Models & Services Germany GmbH). Animals were microchipped (Datamars, Slim Microchip T-SL) after delivery for individual identification. Mice were housed four per cage under a 12 / 12 light / dark cycle with lights turned off at 3:00 PM. Room temperature was controlled at 21°C ± 1°C, and humidity was 60% ± 20%. Mice had ad libitum access to standard rodent chow (KLIBA Nafag 3040 or Altromin 1324, Brogaarden, Denmark) and tap water. Five days before the start of the study, the animals were finally transferred to the HM2-system (a system for real-time monitoring of food intake and drinking) from MBRose (Denmark) to allow for acclimation to the experimental conditions. Animals were uniquely identified using microchips, so each individual animal was identified by its own microchip via the antenna when it entered or exited the food passage. Randomization of mice (n = 8; the youngest was 6 weeks old) for each test group was based on food intake (median value over the last 3 days (24-h interval)) and body weight immediately before the start of the study. A vehicle (50 mM phosphate buffer, pH 7.4, containing 3.5% mannitol)-treated group was included in each experiment. To ensure that each animal had the same nutritional standard, access to food was blocked 8 h before the dark period. Animals were administered a single subcutaneous dose of the test peptide 1 h before the dark period. Food intake was reported hourly over a 24-h period. Food intake was normalized to the mean food intake of the vehicle group and the values ​​are summarized in Table 5 below.

[0150] [Table 11]

[0151] Item A 1. A polypeptide of the general structure of formula (I), or a pharmaceutically acceptable salt thereof: Z1-Z2-Z3 (SEQ ID NO: 647) (I) (In the formula, Z1 has the amino acid sequence Y-Aib-X3-GTFTSDX 10 -SIX 13 -LX 15 -X 16 -X 17 -AX 19 -X 20 -X 21 -FX 23 -X 24 -X 25 -LX 27 -K (SEQ ID NO: 646), wherein X3 is selected as E or D; X 10is 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;X 24 is selected as E or Q;X 25 is selected as W or Y;X 27 is I or L, or Z1 is a derivative thereof having one amino acid substitution; Z2 has 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; or Z2 is a derivative thereof having one amino acid substitution; Z3 is the amino acid sequence X 35 -X 36 -X 37 -X 38 -X 39 -YX 41 -X 42 -X 43 -X 44 -TX 46 -X 47 -X 48 -X 49 wherein X 35 is selected as A, Q, I, V, E or L; X 36 is selected as S, E, T, D or L; X 37is selected as L, Aib, V, D-Leu, I or Tle; X 38 is selected as R, L or Aib; X 39 is selected as H, Aib, D-His, or Tle; X 41 is selected as Y, L, Aib, I or Tle; X 42 is selected as N or Aib;X 43 is selected as W, H, L, R or Aib; X 44 is selected as L, Aib, D-Arg, D-Asp, or Tle; X 46 is selected as R, hArg, or D-Arg; X 47 is selected as Q, bh-Gln, or NMeQ; X 48 is selected as R or NMeR; X 49 is selected as Y, Tle, Chg, D-Tyr, Phg, or Z3 is a derivative thereof having one amino acid substitution. 2. The polypeptide according to item 1, wherein X3 in Z1 is selected as E. 3.X in Z1 10 is selected as Y. 4.X in Z1 13 4. The polypeptide according to any one of items 1 to 3, wherein Aib is selected as Aib. 5.X in Z1 15 is selected as E. 6.X in Z1 16 6. The polypeptide according to any one of items 1 to 5, wherein is selected as K. 7.X in Z1 17 is selected as Q. 8.X in Z1 19 is selected as Q. 9.X in Z1 209. The polypeptide according to any one of items 1 to 8, wherein Aib is selected as Aib. 10.X in Z1 21 is selected as A or E, preferably as A. 11.X in Z1 23 is selected as V. 12.X in Z1 24 is selected as E or Q, preferably as E. 13.X in Z1 25 is selected as W. 14.X in Z1 27 14. The polypeptide according to any one of items 1 to 13, wherein: 15.X in Z2 31 15. The polypeptide according to any one of items 1 to 14, wherein is selected as P. 16.X in Z2 32 16. The polypeptide according to any one of items 1 to 15, wherein: 17.X in Z2 33 is selected as E or S, preferably as S. 18.X in Z2 34 is selected as G. 19.X in Z3 35 is selected as A, Q or V, preferably as A. 20.X in Z3 36 is selected as S. 21.X in Z3 37is selected as I or L, preferably as L. 22.X in Z3 38 22. The polypeptide according to any one of items 1 to 21, wherein is selected as R. 23.X in Z3 39 23. The polypeptide according to any one of items 1 to 22, wherein 24.X in Z3 41 24. The polypeptide according to any one of items 1 to 23, wherein Y is selected as Y. 25.X in Z3 42 25. The polypeptide according to any one of items 1 to 24, wherein N is selected as N. 26.X in Z3 43 26. The polypeptide of any one of items 1 to 25, wherein is selected as W. 27.X in Z3 44 27. The polypeptide according to any one of items 1 to 26, wherein: is selected as L. 28.X in Z3 46 28. The polypeptide according to any one of items 1 to 27, wherein is selected as R. 29.X in Z3 47 is selected as Q or NMeQ, preferably as Q. 30.X in Z3 48 is selected as R or NMeQ, preferably as R. 31.X in Z3 49 is selected as Y. 32.X 35 X 36 X 37 X 38 X 39 32. The polypeptide of any one of items 1 to 31, wherein is selected as ASLRH (SEQ ID NO: 645). 33.X 41X 42 X 43 X 44 33. The polypeptide of any one of items 1 to 32, wherein is selected as YNWL (SEQ ID NO: 326). 34.X 46 X 47 X 48 X 49 34. The polypeptide of any one of items 1 to 33, wherein is selected as RQRY (SEQ ID NO: 327). 35. The polypeptide according to any one of items 1 to 34, wherein the polypeptide is capable of binding to and / or activating GLP-1, GIP and hY2 (hNPY2) receptors.

[0152] Item B 1. A polypeptide of the general structure of formula (I), or a pharmaceutically acceptable salt thereof: Z1-Z2-Z3(I) (In the formula, Z1 is a hybrid polypeptide comprising the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or a derivative thereof having one, two, or three substitutions; Z2 is a linker; Z3 is a polypeptide comprising the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or a derivative thereof having one, two, three, four, or five substitutions. 2. The polypeptide according to claim 1, wherein the linker consists of 1 to 10 amino acid residues. 3. The polypeptide of claim 1 or 2, wherein Z2 has the amino acid sequence GGPSEG (SEQ ID NO: 311) or a derivative thereof having one, two, three or four amino acid substitutions. 4. In Z2, one, two, three or four amino acid substitutions are at positions X 31 , X 32 , X 33 or X 34The polypeptide of claim 3, which is present in any one of the following: 5. Z2 has the amino acid sequence GGX 31 X 32 X 33 X 34 where 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 or Y; X 34 is selected as G, P, Y or A; or Z2 is a derivative thereof having one amino acid substitution. 6. One, two or three substitutions in the derivatives of Z1 are 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 6. The polypeptide according to any one of claims 1 to 5, wherein the polypeptide is present in any one of the following: 7. One, two, three, four or five substitutions in the derivatives of Z3 are 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 7. The polypeptide according to any one of claims 1 to 6, wherein the polypeptide is present in any one of the following: 8. A polypeptide according to any one of claims 1 to 7, wherein the derivative of Z3 has one, two or three substitutions, preferably one or two substitutions, most preferably one substitution. 9. A polypeptide according to any one of claims 1 to 8, wherein the derivative of Z1 has one or two substitutions, preferably one substitution. 10. In the derivatives of Z1, 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 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 10. The polypeptide of claim 1, wherein L is selected as: 11. In the derivatives of Z3, the 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 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 the NMeR; X 49 The polypeptide according to any one of claims 1 to 10, wherein is selected as Tle, Chg, D-Tyr, Phg. 12. The polypeptide is lipidated at a lysine (K) residue, preferably at amino acid position X 28 12. The polypeptide of claim 1, wherein the polypeptide is lipidated at a lysine (K) residue in 13. A polypeptide according to any one of claims 1 to 12, wherein the polypeptide has the general formula LY 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 wherein L is a lipid selected from C18DA or C20DA, and further wherein each Y 1 ~Y 8 are independently selected from absent, [γE], [OEG], [eLys], or [AHX]. 14.C18DA、C18DA[γE]-、C18DA[γE][γE]-、C18DA[γE][γE][γE]-、C18 DA[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、C20 DA[γE]-、C20DA[γE][γE]-、C20DA[γE][γE][γE]-、C20DA[γE][γE][γE][γ E]-、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][eLy s]-、C18DA[γE][γE][eLys]-、C18DA[γE][γE][γE][eLys]-、C18DA[γE][γ E][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][γ E][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]-、C20 DA[OEG][OEG]-、C20DA[γE][OEG][OEG]-、C20DA[γE][γE][OEG][OEG]-、C 20DA[γE][γE][γE][OEG][OEG]-、C20DA[γE][γE][γE][γE][OEG][OEG]-、C20DA[γE][γE][γE][γE][γE][OEG][OEG]-、C18DA[OEG]-、C18DA[γE][γE][OEG]-、C18DA[γE][γE][OEG]-、C18DA[γE][γE][γE][OEG]-、C18DA[γE][γE][γE][γE][OEG]-、C18DA[γE][γE][γE][γE][OEG]-、C18DA[γE][γE][γE][γE][γE][OEG]-、C18DA[γE][γE][γE][γE][γE][OEG]-、C20DA[OEG]-、C20DA[OEG]-、C20DA[OG ][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][OEG]-、C18DA[OEG][eLys]-、C18DA[γE][γE][OEG][eLys]-、C18DA[γE][γE][γE][γE][OEG][eLys]- [OEG][eLys]-、C18DA[γE][γE][γE][γE][γE][OEG][eLys]-、C20DA[OEG][eLys]-、C20DA[γE][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][OEG][eLys]-、C20DA[γE][γE][γE][γE][OEG][eLys]-、C18DA[OEG][OEG][eLys]-、C18 DA[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[γE][OEG][OEG][oEG][eLys]-、C20DA[γE][γE][OEG][OEG][eLys]-、C20DA[γE][γE][OEG][OEG][oEG][eLys]-、C20DA[γE][γE][OEG][OEG][eLys]-、C20DA[γE][γE][OEG][OEG][eLys]-、C20DA[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]-, 14. The polypeptide of any one of claims 1 to 13, selected from the list consisting of C20DA[AHX], C20DA[γE][AHX]-, C20DA[γE][γE][AHX]-, C20DA[γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][AHX]-, C20DA[γE][γE][γE][γE][γE][AHX]-, and C20DA[γE][γE][γE][γE][γE][γE][AHX]-. 15. A polypeptide according to any one of claims 1 to 14, selected from the group consisting of Compound 1 to Compound 305.

[0153] Item C 1. A polypeptide of the general structure of formula (I), or a salt thereof or a pharmaceutically acceptable salt thereof: Z1-Z2-Z3(I) (In the formula, Z1 is a hybrid polypeptide X1-X1 consisting of or comprising the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or a derivative thereof having one, two or three amino acid substitutions. 28 and; Z2 is a peptide X consisting of or comprising the amino acid sequence GGPSEG (SEQ ID NO: 311) or a derivative thereof having one, two, three or four amino acid substitutions. 29 -X 34 and; Z3 is a polypeptide X consisting of or comprising the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or a derivative thereof having one, two, three, four or five amino acid substitutions. 35 -X 49 and; Preferably, Z1-Z2-Z3 has 0, 1, 2, 3, 4, 5 or 6 amino acid substitutions. 2. A polypeptide according to item 1, Z1 consists of or comprises the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or any amino acid position X3, X4, 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 derivatives thereof having one, two or three amino acid substitutions, wherein 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 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 chosen as L; Z2 is the amino acid sequence GGX 31 X 32 X33 X 34 consisting of or comprising: 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; Z3 consists of or comprises the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or any 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 and derivatives thereof having one, two, three, four or five substitutions, wherein the 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 the NMeR; X 49 A polypeptide, wherein: 3. A polypeptide according to item 1 or 2, Z1 consists of or comprises the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or any amino acid position X3, X4, 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 derivatives thereof having one, two or three amino acid substitutions, said substitutions being 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 chosen as L; Z2 is the amino acid sequence GGX 31 -X 32 -X 33 -X 34 consisting of or comprising: 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; Z3 consists of or comprises the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or any 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 and derivatives thereof having one, two or three substitutions, said substitutions being 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 the NMeR. 4. A polypeptide according to any one of items 1 to 3, Z1 consists of or comprises the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or any amino acid position X3, X4, 10 , X 13 , X 15 , X 16 , X 17 , X 21 , X 23 , X 24 or X 25 and derivatives thereof having one, two or three substitutions, said substitutions being 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 23is selected as I;X 24 is selected as Q;X 25 is selected as Y; Z2 is the amino acid sequence GGX 31 -X 32 -X 33 -X 34 consisting of or comprising: 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; Z3 consists of or comprises the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or at any amino acid position X 35 , X 36 , X 37 , X 38 , X 39 , X 41 , X 44 , X 47 , X 48 or X 49 and derivatives thereof having one or two amino acid substitutions, said substitutions being 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 the NMeR. 5. A polypeptide according to any one of items 1 to 4, Z1 consists of or comprises the amino acid sequence Y-Aib-EGTFTSDYSI-Aib-LEKQAQ-Aib-AFVEWLIK (SEQ ID NO: 306), or any amino acid position X21 or X 24 and derivatives thereof having one or two, preferably one, amino acid substitutions, said substitutions being selected as follows: X 21 is selected as A or E; X 24 is selected as E or Q; Z2 consists of or comprises the amino acid sequence GGPSEG (SEQ ID NO: 311) or GGPSSG (SEQ ID NO: 320); Z3 consists of or comprises the amino acid sequence ASLRHYYNWLTRQRY (SEQ ID NO: 307), or any amino acid position X 35 , X 37 , X 47 or X 48 and derivatives thereof having one or two, preferably one, amino acid substitutions, said substitutions being selected as follows: X 35 are selected as Q and V;X 37 is selected as I;X 47 is selected as NMeQ;X 48 is selected as the NMeR.

Claims

1. A polypeptide of the general structure of formula (I): Z1-Z2-Z3(I) (SEQ ID NO: 647) (In the formula, Z1 is the amino acid sequence Y-Aib-X 3 -G-T-F-T-SD-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 X 3 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; 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 I or L; Z2 is the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 wherein X is a linker consisting of 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; Z3 is the 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 is a polypeptide consisting of 35 is selected as A, Q, I, V, E or L; X 36 is selected as S, E, T, D or L; X 37 is selected as L, Aib, V, D-Leu, I, or Tle; 38 is selected as R, L or Aib; X 39 is selected as H, Aib, D-His, or Tle; 41 is selected as Y, L, Aib, I or Tle; X 42 is selected as N or Aib; X 43 is selected as W, H, L, R or Aib; X 44 is selected as L, Aib, D-Arg, D-Asp or Tle; 46 is selected as R, hArg or D-Arg; X 47 is selected as Q, bh-Gln or NMeQ; 48 is selected as R or NMeR; X 49 is selected as Y, Tle, Chg, D-Tyr, Phg.

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

3. In Z1, X 3 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 The polypeptide of claim 1 or 2, wherein is selected as I or L.

4. Z2 is the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 where 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; and preferably 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. 5. A polypeptide according to any one of claims 1 to 4, In Z1, X 3 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; Z2 consists of the amino acid sequence GGPSEG (SEQ ID NO: 311) or GGPSSG (SEQ ID NO: 320); 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 of the general structure of formula (I): Z1-Z2-Z3(I) (In the formula, Z1 is the amino acid sequence X 1 -X 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 one, two, or three amino acid substitutions; Z2 is the amino acid sequence X 29 -X 34 GGPSEG (SEQ ID NO: 311), or a derivative thereof having one, two, three or four amino acid substitutions; Z3 is the amino acid sequence X 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 one, two, three, four, or five amino acid substitutions.

7. 7. The polypeptide of claim 6, In Z1, one, two or three amino acid substitutions are at amino acid position X 3 , 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 substitution is selected as follows: X 3 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; Z2 is the amino acid GGX 31 X 32 X 33 X 34 where 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; In Z3, one, two, three, four or five substitutions are 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 and the substitution is 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; 38 is selected as L or Aib; X 39 is selected as Aib, D-His, or Tle; 41 is selected as L, Aib, I or Tle; 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; 46 is selected as hArg or D-Arg; 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. 7. The polypeptide of claim 6, In Z1, one, two or three amino acid substitutions are at amino acid position X 3 , 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 substitution is selected as follows: X 3 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; Z2 is the amino acid sequence G-G-X 31 -X 32 -X 33 -X 34 where 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; In Z3, one, two or three substitutions are 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 and the substitution is 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; 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 the NMeR.

9. The polypeptide is lipidated at a lysine (K) residue, preferably at amino acid position X 28 9. The polypeptide of claim 1, wherein the polypeptide is lipidated at a lysine (K) residue in

10. 10. The polypeptide of any one of claims 1 to 9, wherein the polypeptide has 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 each Y 1 ~Y 8 are independently absent or selected from [γE], [E], [OEG], [eLys] or [AHX].

11. 11. The polypeptide of any one of claims 1 to 10, wherein the polypeptide has 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 each Y 1 ~Y 8 is independently selected from absent, [γE], [E], [OEG], [eLys], or [AHX], and each Y 1 ~Y 3 is [γE], or each Y 1 ~Y 3 is [E], and Y 4 is selected from [γE], [E], or [OEG], and each Y 5 ~Y 8 are independently absent or selected from [γE], [E], [OEG], [eLys] or [AHX].

12. 12. The polypeptide of any one of claims 1 to 11, selected from the group consisting of compound 2 to compound 305 listed in Table 3.

13. 13. The polypeptide of any one of claims 1 to 12, in the form of a salt or a pharmaceutically acceptable salt.

14. 14. The polypeptide of any one of claims 1 to 13, 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 claims 1 to 14 for use as a pharmaceutical.

16. Overweight, chronic weight management, obesity, symptomatic obesity, eating disorders; Insulin resistance, diabetes, type 1 diabetes, type 2 diabetes, prediabetes; Endocrine obesity: Cushing's syndrome, hypothyroidism, insulinoma, obesity type 2 diabetes, pseudohypoparathyroidism, hypogonadism; Obesity-related endocrine disorders: Polycystic ovary syndrome (PCOS); Central obesity: hypothalamic obesity, frontal lobe syndrome, Klein-Levin syndrome; Genetic obesity: Prader-Willi syndrome, Laurence-Moon-Biedl syndrome; Drug-induced obesity: steroid-induced obesity, phenothiazine-induced obesity, insulin-induced obesity, sulfonylurea-induced obesity, beta-blocker-induced obesity; Comorbidities of obesity and / or overweight: associated type 2 diabetes, associated hypertension, associated NAFLD, associated NASH, associated DKD, associated CKD, associated osteoporosis, associated sleep apnea, associated cancer, associated 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, arteriosclerosis, stroke, heart failure; Kidney disease: diabetic kidney disease (DKD), chronic kidney disease (CKD); Neurodegenerative diseases: Alzheimer's disease, Parkinson's disease; 16. A polypeptide according to any one of claims 1 to 15 for use in a method for the treatment and / or prevention of

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