CN114891071A

CN114891071A - Novel polypeptides and therapeutic uses thereof

Info

Publication number: CN114891071A
Application number: CN202111502870.5A
Authority: CN
Inventors: 韩捷
Original assignee: Hongxu Biotechnology Jiashan Co Ltd
Current assignee: Hongxu Biotechnology Jiashan Co Ltd
Priority date: 2020-12-08
Filing date: 2021-12-07
Publication date: 2022-08-12

Abstract

The present invention relates to novel polypeptides, or pharmaceutically acceptable salts or solvates thereof, having the formula (I) below: H-aib-E-G-T-F-T-S-D-X1-S-X12-X2-L-E-X4-E-A-X5-X6-X3-F-X7-X8-W-L-X9-X11-G-X10(I), the novel polypeptide can be used for treating diabetes and pre-diabetes like GLP-1 medicaments, can reduce the weight and the body fat mass and improve the insulin resistance, has excellent hypoglycemic effect, and has special effect on a high proportion of patients suffering from the diabetes due to excessive weight.

Description

Novel polypeptides and therapeutic uses thereof

Technical Field

The present invention relates to a polypeptide compound and its use in medical treatment.

Background

Metabolic syndrome is a combination of medical conditions that increases the risk of developing type 2 diabetes, atherosclerotic vascular disease, heart disease, and stroke. Medical parameters defining metabolic syndrome include diabetes, impaired glucose tolerance, elevated fasting glucose, insulin resistance, central obesity, hypertension, elevated total cholesterol and triglycerides, elevated low density cholesterol and reduced high density cholesterol. Diabetes includes type one diabetes, type two diabetes, gestational diabetes, etc. According to the data of the World Health Organization (WHO), the prevalence rate of diabetes in developed countries is 5% -10%, and by 2030, the number of diabetes patients in the world is doubled compared with 2000. The number of people with diabetes undiagnosed is over 50% and even more in the pre-diabetic stage than in the diabetic stage worldwide. For example, the number of diabetes mellitus in China reaches 1.14 million, and in addition, 5 million people have low sugar tolerance and impaired sugar regulation function, and the diabetes mellitus patients are about to become. More than half of the patients are unaware that they have become ill. The great risk of diabetes is mainly due to severe complications and high mortality. The data show that diabetes is the leading cause of lower limb amputation and new blindness in adults.

Obesity is a medical condition in which excess fat accumulation in the body can adversely affect health and life expectancy, and has become one of the modern preventable causes of death due to its increasing prevalence in adults and children. It increases the likelihood of a variety of other diseases, including heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis, which are often caused by a combination of excess food intake, reduced energy expenditure, and genetic susceptibility. With the same Body Mass Index (BMI), Asians have higher visceral fat content and consequently have more severe insulin resistance, and type 2 diabetics with normal Asian weight have significantly reduced insulin sensitivity compared to non-diabetic patients. Excess fat causes insulin resistance and beta cell damage, disrupting blood glucose regulation. Various metabolic abnormalities associated with obesity significantly increase the risk of cardiovascular disease. According to clinical statistics, the over 70 percent of patients with type 2 diabetes mellitus suffer from excessive body weight. Therefore, reducing the weight and body fat mass of diabetic patients is an important way to effectively control and even reverse the development of diabetes. The side effects of the existing micromolecular weight-losing medicines are very large. Glucagon-like peptide-1 (GLP-1) receptor agonist drugs can achieve the effect of controlling blood sugar by promoting insulin secretion, improving insulin sensitivity and reducing glucagon release. Thus, GLP-1 drugs are suitable for the treatment of metabolic diseases, especially diabetes. GLP-1 receptor agonists exenatide, liraglutide and the like all show the effect of reducing body weight in animal tests and clinics, and have relatively few side effects. Liraglutide has been approved in the united states for the treatment of diabetes and obesity as the only drug that can be used for both conditions.

However, the existing GLP-1 medicines have the side effect of large gastrointestinal reaction. These side effects affect patient compliance, reducing drug usage and user population. According to the physiological mechanism of a GLP-1 receptor, the GLP-1 medicament has slow effect on weight reduction, and a large dose higher than that of diabetes treatment is needed when obesity is clinically treated, so that the side effect of large gastrointestinal reaction is more prominent. The weight loss of most patients is not more than 5% on average, and the weight rebound is obvious after stopping taking the medicine.

Therefore, there is a clinical need for a drug that can lower blood glucose, lower body fat, and reduce weight.

Diabetics are at higher risk of developing cardiovascular disease and, therefore, need strict control of blood lipid levels. Clinical studies have shown that long-term use of statins may increase the risk of diabetes in the user. Statins and fibrates have obvious side effects and are not tolerant. The non-alcoholic fatty liver does not have a therapeutic drug with ideal curative effect at present. The compound of the invention can not only reduce blood sugar, but also obviously reduce triglyceride and total cholesterol, is hopeful to simultaneously solve the two problems of hyperglycemia, hyperlipidemia and hyperglycemia in hypertension, and is expected to have obvious benefits on cardiovascular health of users. The polypeptide of the invention is more suitable for diabetics or people in the early stage of diabetes than statins. The polypeptides of the invention may provide a new option for the treatment of these diseases. The polypeptide of the present invention is suitable for various diseases caused by abnormal lipid metabolism, including hyperlipidemia, non-alcoholic fatty liver disease, etc. The polypeptide of the invention can also be used for diseases such as hypertension, arteriosclerosis, coronary heart disease, peripheral artery disease, stroke and the like or any combination of the diseases.

The majority of diabetics are middle-aged and elderly people and need to take various medicines. This necessarily involves compatibility and matching between the drugs. Besides the drug cross reaction and the possibility of more toxic and side effects caused by multiple drugs, different drugs have different effective time and different taking frequency, which also increases the trouble for patients. Therefore, the polypeptide of the invention is not only beneficial to enhancing the curative effect and reducing the toxic and side effects, but also convenient for patients, thereby improving the treatment effect.

The polypeptide of the invention can also be used in the treatment of diabetes as a GLP-1 class drug. Because the polypeptides reduce the weight and the body fat and improve the insulin resistance, the polypeptide has excellent hypoglycemic effect and special effect on a high proportion of patients suffering from diabetes due to excessive weight. Although many people with excessive weight or obesity in the population are not medically identified as diabetic patients, the pre-diabetic symptoms such as glucose intolerance and postprandial hyperglycemia appear, and the polypeptide is also suitable for the pre-diabetic population.

Disclosure of Invention

In one aspect, the present invention relates to a peptide compound having formula (I) or a pharmaceutically acceptable salt or solvate thereof,

H-aib-E-G-T-F-T-S-D-X1-S-X12-X2-L-E-X4-E-A-X5-X6-X3-F-X7-X8-W-L-X9-X11-G-X10(I)

wherein, X1 represents an amino acid selected from L, V or Y, X2 represents an amino acid selected from Q, A, aib or Y, X3 represents an amino acid selected from L, E or D, X4 represents an amino acid selected from E or K, X5 represents an amino acid selected from V or a, X6 represents an amino acid selected from K, R or Q, X7 represents an amino acid selected from I or V, X8 represents an amino acid selected from E, N or a, X9 represents an amino acid selected from K, V, I or L, X10 represents absent or GPSSGAPPP, GPPSGAPPP, GPSSGKPPP, GPSSGEPPP, GPSSaibAPPP, GPSSGAPP, GPSSGAP, GPSSGA, GPSSG, GPSS, GPS, GP, G or RG; x11 represents an amino acid of N or A or K; x12 represents an amino acid of I, S or K;

optionally, one or two amino acids selected from S or amino or thiol containing side chain are added at C-terminus of X10, and the carboxyl group of the C-terminal amino acid is optionally amidated as a C-terminal amide, the amino acid having a structure represented by formula (II) or formula (III):

wherein the wavy line represents the point of attachment to the adjacent group, n1 is an integer of 1 to 7, and the carboxyl moiety thereof is COOH or CONH when formula (II) or formula (III) is a C-terminal amino acid ₂ (ii) a Preferably, the amino acid containing a side chain amino group is lysine; preference is given toIn addition, the amino acid containing a side chain thiol group is cysteine,

optionally, the amino acid containing a side chain amino group added at the C-terminus of X10 is modified at its side chain amino group or the amino acid containing a side chain thiol group at its side chain thiol group with a long-acting group, preferably, the long-acting group has the structure of formula (IV):

O1-O2-O3-O4-O5-O6-O7-O8-(IV)，

wherein O1 represents a structure of formula (V) or (VI):

wherein n2 is an integer of 6 to 24, preferably 10 to 24, further preferably 16 to 22;

wherein the wavy line represents the point of attachment of an amino group to an adjacent group, O2-O3-O4-O5-O6-O7-O8-represents a linker, wherein each of O2 to O8 is independently represented by any one of the following amino acid residues or long chain structures: a-Glu, γ -Glu, α -Asp, β -Asp, α -hGlu, δ -hGlu, Gly, Ala, β -Ala, GABA or PEG2, or one or more of O2 to O8 is absent, provided that at least two of O2 to O8 are present, preferably at least one negatively charged moiety is contained in O2 to O8.

A peptide compound according to any one of the preceding aspects, wherein O2-O3-O4-O5-O6-O7-O8-represents a linker selected from the group consisting of: gamma Glu-PEG 2-gamma Glu-, gamma Glu-PEG2-2 Xgamma Glu-, gamma Glu-PEG2-, gamma Glu-2 XPEG 2-, 7Glu-3 XPEG 2-, gamma Glu-PEG 2-gamma Glu-PEG2-, gamma Glu-2 XPEG 2-gamma Glu-, gamma Glu-2 XPEG 2-2 Xgamma Glu-, 2 Xgamma Glu-PEG2-, 2 Xgamma Glu-PEG 2-gamma Glu-, 2 Xgamma Glu-PEG 2-gamma Glu-PEG2-, 2 Xgamma Glu-2 XPEG 2-, 2 Xgamma Glu-2 XPEG 2-gamma Glu-, 2 Xgamma Glu-2 XPEG 2-2 Xgamma Glu-.

A peptide compound according to any one of the preceding aspects, in some embodiments, wherein O2-O3-O4-O5-O6-O7-O8-represents a linker γ Glu-PEG2-, γ Glu-2 × PEG2-, γ Glu-3 × PEG2-, O1 represents a structure of formula (V) or (VI).

A peptide compound according to any one of the preceding aspects, in some embodiments, wherein O2-O3-O4-O5-O6-O7-O8-represents a linker selected from the group consisting of gamma Glu-PEG2-, gamma Glu-2 × PEG2-, gamma Glu-3 × PEG2-, O1 represents a structure of formula (V).

A peptide compound according to any one of the preceding aspects, in some embodiments, wherein O2-O3-O4-O5-O6-O7-O8-represents a linker γ Glu-2 × PEG2-, γ Glu-3 × PEG2-, O1 represents a structure of formula (V).

A peptide compound according to any one of the preceding aspects, in some embodiments, wherein O2-O3-O4-O5-O6-O7-O8-represents linker gammaglu-2 × PEG2-, and O1 represents a structure of formula (V).

A peptide compound according to any one of the preceding aspects, in some embodiments, wherein O2-O3-O4-O5-O6-O7-O8-represents a linker gammaglu-2 xpeg 2-, O1 represents a structure of formula (V) wherein n2 is an integer from 16 to 22.

Optionally, the side chain mercapto group-containing amino acid added at the C-terminal of X10 is modified at its side chain mercapto group by a long-acting group of formula (IV), and optionally, a reactive group capable of reacting with the mercapto group to form a covalent bond may be added between the side chain mercapto group of the C-terminal amino acid and the long-acting group as required.

In some embodiments, the lysine side chain amino group is conjugated to a long-acting group, the molecular structure referred to herein as K (x18), having the structure of formula (VIII):

in some embodiments, the lysine side chain is conjugated to a long-acting group, the molecular structure of which is abbreviated herein as K (x20), having the structure of formula (IX):

wherein the wavy line represents the point of attachment to the adjacent amino acid residue.

In some embodiments, the linkage between the side chain thiol group and the long-acting group of the side chain thiol group-containing amino acid is: side chain thiol-thiol reactive group-optional linking group L-long acting group of amino acid containing side chain thiol.

In some embodiments, the side-chain thiol group of the side-chain thiol-containing amino acid is attached to one end of a linking group L by reaction with a michael reaction acceptor (e.g., maleimide or vinylsulfone) or a thiol-reactive group (e.g., iodoacetic acid or bromoacetic acid), preferably the other end of the linking group L further forms a covalent bond with the long-acting group of formula IV.

In some embodiments, the linking group L is- (CH) ₂ ) _n3 -and- (CH) ₂ CH ₂ O) _n 4-long chains formed by arranging and combining according to the structural requirements and connecting together through covalent bonds; or- (CH) ₂ ) _n3 -、-(CH ₂ CH ₂ O) _n4 -optionally containing an amino or carboxyl group at one or both ends, a long chain linked together by an amide bond, e.g. the linking group L is selected from-NH- (CH) ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -，-NH-(CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -NH-，-NH- (CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -CO-，-NH-(CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -NHCO-(CH ₂ ) _n8 -，-NH-(CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 - (CH ₂ ) _n7 -NHCO-(CH ₂ ) _n8 -NH-, or any combination thereof, wherein n3, n4, n5, n6, n7, n8 are each integers from 0 to 10, such as 0, 1, 2, 3, 4,5, 6, 7,8, 9, 10.

In some embodiments, L is-NH-CH ₂ -(CH ₂ CH ₂ O) ₃ -(CH ₂ ) ₃ -NH-。

In some embodiments, non-limiting illustrative examples of Michael reaction acceptors or thiol-reactive groups attached to linking group L include

The structure of the above exemplary michael reaction acceptor or thiol-reactive group after reaction with a side-chain thiol group of an amino acid containing a side-chain thiol group is as follows:

the wavy line is the point of attachment to the long-acting group of formula (IV), for example, to O8. Is the point of attachment of the side-chain thiol group of the amino acid containing the side-chain thiol group to the other part of the amino acid.

Optionally, any one of the amino acids in the polypeptide fragment represented by X10 may be substituted with an amino acid having an amino group or a thiol group in the side chain, the amino acid having the structure of formula (II) or formula (III). Optionally, the amino acid containing a side chain amino group is modified at its side chain amino group with a long-acting group, preferably the long-acting group has the structure of formula (IV); optionally, the amino acid containing side chain sulfhydryl group is modified by long-acting group at side chain sulfhydryl group, preferably, the long-acting group has the structure of formula (IV), and optionally, a reactive group capable of reacting with sulfhydryl group to generate covalent bond can be added between side chain sulfhydryl group and long-acting group according to requirement.

In some embodiments, the cysteine side chain thiol is conjugated to a long-acting group, herein abbreviated as C (x18), having the structure of formula (IX):

in some embodiments, the cysteine side chain thiol is conjugated to a long-acting group, herein abbreviated as C (X20), having the structure of formula (X):

wherein the wavy line represents the point of attachment to an adjacent group.

Optionally, the polypeptide fragment GPPSGAPPP, GPSSGKPPP, GPSSGEPPP, GPSSaibAPPP represented by X10 may be reduced by 1, 2, 3, 4,5, 6, 7,8 amino acids from the C-terminus of the fragment to the N-terminus of the fragment.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L.

The peptidic compound according to any of the preceding aspects, in some embodiments, X1 is Y.

The peptidic compound according to any of the preceding aspects, in some embodiments, Xl is V.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q.

The peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Y.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Aib.

The peptidic compound according to any of the preceding aspects, in some embodiments, X3 is D.

A peptidic compound according to any of the preceding aspects, in some embodiments, X3 is E.

A peptidic compound according to any of the preceding aspects, in some embodiments, X3 is L.

A peptidic compound according to any of the preceding aspects, in some embodiments, X4 is E.

The peptidal compound according to any of the preceding aspects, in some embodiments, X4 is K.

A peptidic compound according to any of the preceding aspects, in some embodiments, X5 is V.

The peptide compound according to any one of the preceding aspects, in some embodiments, X5 is a.

A peptidic compound according to any of the previous aspects, in some embodiments, X6 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X6 is R.

A peptidic compound according to any of the preceding aspects, in some embodiments, X6 is Q.

A peptidic compound according to any of the preceding aspects, in some embodiments, X7 is I.

A peptidic compound according to any of the preceding aspects, in some embodiments, X7 is V.

A peptidic compound according to any of the preceding aspects, in some embodiments, X8 is E.

The peptidic compound according to any of the preceding aspects, in some embodiments, X8 is N.

The peptide compound according to any one of the preceding aspects, in some embodiments, X8 is a.

A peptidic compound according to any of the preceding aspects, in some embodiments, X9 is I.

A peptidic compound according to any of the preceding aspects, in some embodiments, X9 is L.

The peptidal compound according to any of the preceding aspects, in some embodiments, X9 is K.

A peptidic compound according to any of the preceding aspects, in some embodiments, X9 is Aib.

A peptidic compound according to any of the preceding aspects, in some embodiments, X9 is V.

A peptidic compound according to any of the previous aspects, in some embodiments, X10 is absent.

The peptidal compound according to any of the preceding aspects, in some embodiments, X10 is GPSSGAPPPSK.

The peptide compound according to any one of the preceding aspects, in some embodiments, X10 is GPSSGAPPPSC.

A peptidal compound according to any of the preceding aspects, in some embodiments, X10 is GPSSGAPPPS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X10 is GPSSGAPPPK.

The peptide compound according to any one of the preceding aspects, in some embodiments, X10 is GPSSGAPPPC.

The peptidal compound according to any of the preceding aspects, in some embodiments, X10 is GPSSGAPPP.

The peptidal compound according to any of the preceding aspects, in some embodiments, Xi0 is GPSSGAPP.

The peptidal compound according to any of the preceding aspects, in some embodiments, X10 is GPSSGAP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X10 is gps sga.

A peptidic compound according to any of the preceding aspects, in some embodiments, X10 is GPSSG.

A peptidic compound according to any of the preceding aspects, in some embodiments, X10 is GPSS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X10 is GPS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X10 is GP.

The peptidal compound according to any of the preceding aspects, in some embodiments, X10 is G.

The peptidic compound according to any of the preceding aspects, in some embodiments, X11 is N.

The peptide compound according to any one of the preceding aspects, in some embodiments, X11 is a.

The peptidal compound according to any of the preceding aspects, in some embodiments, X11 is K.

A peptidic compound according to any of the preceding aspects, in some embodiments, X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X12 is S.

The peptidal compound according to any of the preceding aspects, in some embodiments, X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X10 is GPSSGAPPPC.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and XI0 is GPSSGAPPP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and XI0 is GPSSGAPP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X10 is GPSSGAP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X10 is gps sga.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X10 is GPSSG.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and XI0 is GPSS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X10 is GPS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X10 is GP.

The peptidal compound according to any of the preceding aspects, in some embodiments, X1 is L and X10 is G.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is Q and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is Q and X10 is GPSSGAPPPC.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is a and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is a and X10 is GPSSGAPPPC.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is Q and X10 is GPSSGAPPP.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q and X10 is GPSSGAPP.

The peptidal compound according to any of the preceding aspects, in some embodiments, X2 is Q and X10 is GPSSGAP.

The peptidal compound according to any of the preceding aspects, in some embodiments, X2 is Q and X10 is gps sga.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q and X10 is GPSSG.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q and X10 is GPSS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q and X10 is GPS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q and X10 is GP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q and X10 is G.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is a and X10 is GPSSGAPPP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is gps sgapp.

The peptidal compound according to any of the preceding aspects, in some embodiments, X2 is a and X10 is gps sgap.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is gps sga.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is GPSSG.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is GPSS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is GPS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is GP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X10 is G.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib and X10 is GPSSGAPPP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is GPSSGAPP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is GPSSGAP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is gps sga.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is GPSSG.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is GPSS.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib and X10 is GPS.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is GP.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X10 is G.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q and X12 is I.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q and X12 is S.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is a and X12 is I.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X12 is S.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X12 is K.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib and X12 is I.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X12 is S.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X12 is K.

The peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L and X2 is Q.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X2 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L and X2 is aib.

The peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L and X2 is Y.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPSSGAPPP.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPSSGAPP.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPSSGAP.

A peptidal compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is gps sga.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPSSG.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPSS.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is GP.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X10 is G.

A peptidal compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is gps gappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is GPSSGAPPP.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is gps sgapp.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is gps gap.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is gps sga.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is GPSSG.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is GPSS.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X1 is L, X2 is a, and X10 is GPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is GP.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X10 is G.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X1 is L, X2 is aib, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is GPSSGAPPP.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is GPSSGAPP.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is GPSSGAP.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is gps sga.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is GPSSG.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is GPSS.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X1 is L, X2 is aib, and X10 is GPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is GP.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X10 is G.

A peptidal compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Y, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, and X10 is gps gappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X1 is L, X2 is a, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is E, X5 is V, X10 is GPSSGAPPPS, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is E, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is E, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is E, X5 is V, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is E, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is E, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is E, X5 is V, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is E, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is E, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, X5 is V, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, X5 is V, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, X5 is V, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, X5 is V, and X10 is GPSSGAPPPC.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, X5 is V, X7 is I, and X10 is gps gappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is E, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is E, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is K, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is K, X5 is V, and X7 is I.

The peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q and X9 is L.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q and X9 is V.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q, X9 is L, and X11 is a.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is Q, X9 is L, and X11 is K.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q, X9 is I, and X11 is a.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Q, X9 is I, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q, X9 is V, and X11 is a.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is Q, X9 is V, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Q, X9 is K, and X11 is a.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X9 is L.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X9 is I.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X9 is V.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X9 is L.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X9 is I.

The peptidic compound according to any of the preceding aspects, in some embodiments, X2 is a and X9 is V

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a and X9 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is L, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is L, and X11 is N.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is L, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is I, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is I, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is I, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is V, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is V, and X11 is N.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is V, and X11 is K.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is a, X9 is K, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X9 is L.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X9 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X9 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, and X9 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, and X9 is K.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib and X9 is L.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib and X9 is I.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X9 is V

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib and X9 is K.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib, X9 is L, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib, X9 is L, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib, X9 is L, and X11 is K.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib, X9 is I, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib, X9 is I, and X11 is N.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X2 is aib, X9 is I, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib, X9 is V, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib, X9 is V, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib, X9 is V, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is aib, X9 is K, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X9 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X9 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, and X9 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, and X9 is K.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X9 is L, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X9 is L, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X9 is L, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X5 is V, X9 is L, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X5 is V, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X5 is V, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X9 is L, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X9 is L, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X7 is I, X9 is L, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X7 is I, X9 is L, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X3 is L, X4 is K, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X3 is L, X4 is K, X5 is V, X6 is R, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, and X8 is E.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X2 is Q, and X4 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, X7 is I, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X7 is I, and X10 is gps sgappps.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X7 is I, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, X7 is I, and X10 is GPSSGAPPPC.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X7 is I, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X7 is I, and X10 is GPSSGAPPPK.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, X7 is I, and X10 is GPSSGAPPPC.

The peptidic compound according to any of the preceding aspects, in some embodiments, X9 is L and X11 is N.

The peptide compound according to any one of the preceding aspects, in some embodiments, X9 is L and X11 is a.

The peptidal compound according to any of the preceding aspects, in some embodiments, X9 is L and X11 is K.

The peptidic compound according to any of the preceding aspects, in some embodiments, X9 is I and X11 is N.

The peptidic compound according to any of the preceding aspects, in some embodiments, X9 is I and X11 is a.

The peptidic compound according to any of the preceding aspects, in some embodiments, x9 is I and x11 is K.

The peptide compound according to any one of the preceding aspects, in some embodiments, X9 is V and X11 is N.

The peptide compound according to any one of the preceding aspects, in some embodiments, X9 is V and X11 is a.

The peptide compound according to any one of the preceding aspects, in some embodiments, X9 is V and X11 is K.

The peptide compound according to any one of the preceding aspects, in some embodiments, X9 is K and X11 is a.

The peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Y and X9 is L.

The peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Y and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Y, X9 is L, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Y, X9 is L, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Y, X9 is L, and X11 is K.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Y, X9 is I, and Xl1 is N.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Y, X9 is I, and X11 is a.

A peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Y, X9 is I, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Y, X9 is V, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Y, X9 is V, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Y, X9 is V, and X11 is K.

The peptide compound according to any one of the preceding aspects, in some embodiments, X2 is Y, X9 is K, and X11 is a.

The peptidic compound according to any of the preceding aspects, in some embodiments, X1 is Y and X2 is Q.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is Y and X2 is a.

The peptide compound according to any one of the preceding aspects, in some embodiments, X1 is Y and X2 is Aib.

The peptidic compound according to any of the preceding aspects, in some embodiments, X1 is Y and X2 is Y.

The peptidal compound according to any of the preceding aspects, in some embodiments, X4 is K and X9 is L.

The peptide compound according to any one of the preceding aspects, in some embodiments, X4 is K and X9 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is Y, X4 is K, and X9 is L.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is Y, X2 is Y, and X4 is E.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is Y, X2 is Y, and X4 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is Y, X2 is Y, X4 is K, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is Y, X2 is Y, X4 is K, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X3 is L, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X3 is L, X5 is V, X7 is I, and X8 is E.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X3 is L, X5 is V, X6 is R, X7 is I, and X8 is E.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, and X8 is E.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X11 is a, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X11 is N, and X12 is K.

The peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L and X9 is I.

The peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X5 is V, and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is E, X5 is V, and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X4 is K, X5 is V, X7 is I, X8 is E, and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X4 is E, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is E, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is E, X5 is V, X7 is I, and X8 is E.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, and X8 is E.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X4 is E, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X3 is L, X4 is E, X5 is V, and X7 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X3 is L, X4 is E, X5 is V, X7 is I, and X8 is E.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, and X8 is E.

The peptidic compound according to any of the preceding aspects, in some embodiments, X2 is Y and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Y, X4 is K, and X5 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, and X9 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X11 is K and X9 is not K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X9 is L.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X9 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X9 is V.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X11 is K and X9 is not K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is I, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is I, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is I, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is V, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is V, and X11 is N.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, X9 is V, and X11 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is I, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X11 is a, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X11 is N, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is V, X11 is K, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, X11 is a, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X11 is a, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X11 is N, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is V, X11 is K, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, X11 is N, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, X11 is a, and X12 is K.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, X11 is N, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is K, X11 is N, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is aib, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is Q, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X2 is a, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X11 is a, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X10 is GPSSGAPPPK, X11 is a, and X12 is I. Optionally, the C-terminal lysine of X10 is modified at its side chain amino group with a long-acting group. Preferably, the long-acting group has the structure of formula (IV).

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X10 is GPSSGAPPPK, X11 is a, and X12 is I. Optionally, the C-terminal lysine of X10 is modified at its side chain amino group with a long-acting group. Preferably, the long-acting group has the structure of formula (IV). A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X10 is GPSSGAPPPK, X11 is a, and X12 is I. Optionally, the C-terminal lysine side chain amino group of X10 is conjugated with long-acting group, and the molecular structure is K (X18) or K (X20).

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X10 is gps gappps, X11 is a, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X10 is GPSSGAPPPS.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, and X10 is GPSSGAPPPK. Optionally, the C-terminal lysine of X10 is modified at its side chain amino group with a long-acting group. Preferably, the long-acting group has the structure of formula (IV).

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X10 is gps gappps, and X11 is a.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, X8 is E, X9 is L, X10 is GPSSGAPPPK, and X11 is a. Optionally, the C-terminal lysine of X10 is modified at its side chain amino group with a long-acting group. Preferably, the long-acting group has the structure of formula (IV).

A peptidic compound according to any of the previous aspects, in some embodiments, X4 is E and X12 is I.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X4 is E, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X4 is E, X5 is V, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is E, X5 is V, X6 is R, X7 is I, and X12 is I.

The peptidic compound according to any of the preceding aspects, in some embodiments, X4 is K and X12 is I.

A peptidic compound according to any of the preceding aspects, in some embodiments, X1 is L, X4 is K, and X12 is I.

A peptide compound according to any one of the preceding aspects, wherein in some embodiments, X1 is L, X4 is K, X5 is V, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, and X12 is I.

A peptide compound according to any one of the preceding aspects, in some embodiments, X1 is L, X3 is L, X4 is K, X5 is V, X6 is R, X7 is I, and X12 is I.

The peptide compound according to any one of the preceding aspects, wherein said peptide compound is selected from the group consisting of:

compound 1, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 2.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 3.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 4.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound (I)5.H(aib)EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 6.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPC (x18) -NH ₂

Compound 7.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPS-NH ₂

Compound 8.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPSK-NH ₂

Compound 9.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPSK (x18) -NH ₂

Compound 10, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPK-NH ₂

Compound 11.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPK (x18) -NH ₂

Compound 12.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPC-NH ₂

Compound 13.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLINGGPSSGAPPPS-NH ₂

Compound 14.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLIAGGPSSGAPPPS-NH2

Compound 15.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 16.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 17.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPSK (x18) -NH ₂

Compound 18.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 19.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 20.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 21.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVNGGPSSGAPPPS-NH ₂

Compound 22.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVNGGPSSGAPPPK-NH2

Compound 23.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVAGGPSSGAPPPS-NH ₂

Compound 24.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVAGGPSSGAPPPSK-NH ₂

Compound 25.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVAGGPSSGAPPPK-NH ₂

Compound 26.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVKGGPSSGAPPPS-NH ₂

Compound 27.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPS-NH ₂

Compound 28.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPK-NH2

Compound 29, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPSK-NH ₂

Compound 30.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 31.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 32.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 33.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 34.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 35.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPSK (x18) -NH ₂

Compound 36.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPSC-NH ₂

Compound 37.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 38.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 39.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 40.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 41, H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPSK-NH2

Compound 42.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPSK (x18) -NH ₂

Compound 43.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPSC-NH ₂

Compound 44.H (aib) EGTFTSDLSK(aib) LEEEAVRLFFIEWLKNGGPSSGAPPPK-NH ₂

Compound 45.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 46, H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 47.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 48.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 49.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPSK (x18) -NH ₂

Compound 50.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 51.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 52.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 53.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 54.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 55, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 56.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 57.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 58.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPC (x18) -NH ₂

Compound 59.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 60.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 61.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 62.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 63.H (aib) EGTFTSDLSKALEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 64.H (aib) EGTFTSDLSKALEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 65.H (aib) EGTFTSDLSIALEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 66.H (aib) EGTFTSDLSIALEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 67, H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGAPPPS-NH2

Compound 68.H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 69.H (aib) EGTFTSDLSKQLEEEAVKEFIEWLKNGGPSSGAPPPS-NH ₂

Compound 70.H (aib) EGTFTSDLSKQLEEEAVKEFLAWLKNGGPSSGAPPPS-NH ₂

Compound 71.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPSK-NH ₂

Compound 72.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPK-NH ₂

Compound 73.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 74.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPC-NH ₂

Compound 75.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKAGGPSSGAPPPS-NH ₂

Compound 76.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNNGGPSSGAPPPS-NH ₂

Compound 77.H (aib) EGTFTSDYSKQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 78.H (aib) EGTFTSDYSIQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 79.H (aib) EGTFTSDVSSYLLEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 80.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 81, H (aib) EGTFTSDLSKYLEEEAVKLFIEWLKNGGPSSGA-NH ₂

Compound 82.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPK (x20) -NH ₂

Compound 83.H (aib) EGTFTSDLSKYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 84.H (aib) EGTFTSDLSKYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 85.H (aib) EGTFTSDLSKYLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 86.H (aib) EGTFTSDYSKQLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 87.H (aib) EGTFTSDYSKQLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 88.H (aib) EGTFTSDYSKQLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 89.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 90.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 91, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 92.H (aib) EGTFTSDYSIYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 93.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 94.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 95.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH2

Compound 96.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 97, H (aib) EGTFTSDLSIQLEKEAVLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 98.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 99.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 100.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 101, H (aib)EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 102.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 103, H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 104.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPC (x18) -NH ₂

Compound 105, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 106.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPSC-NH ₂

Compound 107.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 108.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 109.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 110.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 111.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPSC-NH ₂

Compound 112, H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 113.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 114.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 115.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLVKGRG-NH ₂

Compound 116.H (aib) EGTFTSDLSIALEKEAVKLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 117.H (aib) EGTFTSDLSIALEKEAVKLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 118.H (aib) EGTFTSDLSIALEKEAVKLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 119, H (aib) EGTFTSDLSI(aib) LEKEAVKLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 120.H (aib) EGTFTSDLSI(aib) LEKEAVKLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 121, H (aib) EGTFTSDLSI(aib) LEKEAVKLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 122, H (aib) EGTFTSDLSIQLEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 123.H (aib) EGTFTSDLSIALEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 124.H (aib) EGTFTSDLSI(aib) LEKEAVRLFVNWLLAGGPSSGAPPPC-NH ₂

Compound 125.H (aib) EGTFTSDLSI(aib) LEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 126.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 127.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPK (x18) -NH ₂

Compound 128.H (aib) EGTFTSDLSIALEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 129, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 130.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 131, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 132.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 133, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPSC-NH ₂

Compound 134, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 135, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 136.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPK (x18)

Compound 137.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 138.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 139.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 140.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 141, H (aib) EGTFTSDYSKYLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 142, H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 143.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 144.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 145.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPK-NH ₂

Compound 146.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPSK-NH ₂

Compound 147, H (aib) EGTFTSDYSIYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 148.H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 149, H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 150.H (aib) EGTFTSDLSKQLEEEAVRLFVNWLKNGGPSSGAPPPS-NH ₂

Compound 151, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 152.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 153, H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 154.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 155.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 156.H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 157.H (aib) EGTFTSDYSYRYLEEAVRLFIEWLKAGGPSSGAPPPS-NH ₂

Compound 158, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSS-NH ₂

Compound 159.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 160.H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 161, H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 162.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 163, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPS-NH ₂

Compound 164.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 165, H (aib) EGTFTSDLSKALEKEAVRLFIEWLKNGGPSSGAP-NH ₂

Compound 166.H (aib) EGTFTSDLSSYLEEEAVRLFIEWLKNGGPSSGAPP-NH ₂

Compound 167.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPP-NH ₂

Compound 168, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAP-NH ₂

Compound 169, H (aib) EGTFTSDLSKQLEEEAVKLFIAWLKNGGPSSGAPPPS-NH ₂

Compound 170.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVKGRG-NH ₂

Compound 171, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPK-NH ₂

Compound 172, H (aib) EGTFTSDLSKALEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 173.H (aib) EGTFTSDLSIALEEEAVRLFIEWLVKGRG-NH ₂

Compound 174.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLIAGGPSSGAPPPS-NH ₂

Compound 175.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 176.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLLAGGPSSGAPPPS-NH ₂

Compound 177.H (aib) EGTFTSDLSKYLEEEAVRLFIAWLIAGGPSSGAPPPS-NH ₂

Compound 178, H (aib) EGTFTSDLSKALEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 179.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 180.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 181.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 182.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPK-NH ₂

Compound 183, H (aib) EGTFTSDLSKYLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 184, H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 185.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 186.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 187.H (aib) EGTFTSDLSIQLEKEAVRLFIAWLKNGGPSSGAPPPS-NH ₂

Compound 188.H (aib) EGTFTSDYSIQLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 189, H (aib) EGTFTSDLSIALEKEAVRLFIEWLVKGRG-NH ₂

Compound 190.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 191, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 192.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 193.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 194, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGG-NH ₂

Compound 195, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPK-NH ₂

Compound 196, H (aib) EGTFTSDLSKQLEEEAVRLFIAWLVKGGPSSGAPPPS-NH ₂

Compound 197.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 198, H (aib) EGTFTSDLSIQLEEEAVKEFIAWLKNGGPSSGAPPPS-NH ₂

Compound 199.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLVKGRG-NH ₂

Compound 200.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 201, H (aib) EGTFTSDLSKOLEEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 202, H (aib) EGTFTSDLSKALEEEAVRLFIEWLVKGGPSSGAPPPS-NH ₂

Compound 203, H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSS-NH ₂

Compound 204.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 205.H (aib) EGTFTSDLSIALEKEAVKEFIAWLVKGGPSSGAPPPS-NH ₂

Compound 206, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 207, H (aib) EEGTFTSDLSIQLEEEAVRLFIEWLLAGGPSS-NH2

Compound 208.H (aib) EGTFTSDYSIQLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 209, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAK-NH ₂

Compound 210.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 211, H (aib) EGTFTSDYSIALEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 212, H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSG-NH ₂

Compound 213, H (aib) EGTFTSDYSKYLEEEAVKEFIAWLKNGGPSSGAPPPS-NH ₂

Compound 214.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 215.H (aib) EGTFTSDVSSYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 216.H (aib) EGTFTSDYSIYLEKEAVRLFIEWＬLAGGPSS-NH ₂

Compound 217, H (aib) EGTFTSDLSIYLEEEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 218, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 219.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPK-NH ₂

Compound 220.H (aib) EGTFTSDYSIYLEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 221, H (aib) EGTFTSDLSIALEKEAVKEFIAWLLAGGPSSGAPPPS-NH ₂

Compound 222, H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 223H (aib) EGTFTSDYSIYLEEEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 224.H (aib) EGTFTSDLSKALEEEAVRLFIEWLVKGGPSSGAPPPK-NH ₂

Compound 225.H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 226, H (aib) EGTFTSDLSK(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 227, H (aib) EGTFTSDYSIYLEEEAVKEFIAWLLAGGPSSGAPPPS-NH ₂

Compound 228, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 229, H (aib) EGTFTSDYSIALEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 230.H (aib) EGTFTSDLSIALEKEAVRLFVNWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 231, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 232, H (aib) EGTFTSDLSIALEKEAVKEFVEWLLAGG-NH ₂

Compound 233, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 234, H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 235.H (aib) EGTFTSDLSIYLEEEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 236.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 237, H (aib) EGTFTSDYSKALEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 238.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 239, H (aib) EGTFTSDLSIYLEKEAVKLFVNWLLAGGPSSG-NH ₂

Compound 240.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 241, H (aib) EGTFTSDYSIQLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 242, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 243, H (aib) EGTFTSDYSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 244.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 245.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPK-NH2

Compound 246.H (aib) EGTFTSDYSIYLEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 247.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 248, H (aib) EGTFTSDLSI(aib) LEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 249.H (aib) EEGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 250, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGA-NH ₂

Compound 251, H (aib) EGTFTSDLSIYLEEEAVRLFVNWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 252, H (aib) EGTFTSDLSK(aib) LEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 253, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 254, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLKNGGPSSGAPPPS-NH ₂

Compound 255, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 256.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPK (x20) -NH ₂

Compound 257, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLKNGGGPSSGAPPPK (x18) -NH ₂

Compound 258, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 259, H (aib) EGTFTSDLSKALEEEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 260.H (aib) EGTFTSDLSKYLEKEAVRLFVNWLKNGGPSSGAPPPS-NH ₂

Compound 261, H (aib) EGTFTSDLSIQLEKEAVQDFVNWLLAGGPSSGAPPPK-NH ₂

Compound 262.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 263.H (aib) EGTFTSDLSKQLEEEAVQDFVNWLKNGGPSSGAPPPS-NH ₂

Compound 264, H (aib) EGTFTSDLSK(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 265.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPK-NH ₂

Compound 266, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 267.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPK (x20) -NH ₂

Compound 268.H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSS-NH ₂

Compound 269.H (aib) EGTFTSDYSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 270.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 271, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 272.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 273.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK (x 2)0)-NH ₂

Compound 274.H (aib) EGTFTSDLSIQLEKEAVQDFVNWLLAGGPSSGAPPPS-NH ₂

Compound 275.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 276.H (aib) EGTFTSDLSSALEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 277, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPK (x20) -NH ₂

Compound 278.H (aib) EGTFTSDLSKQLEEEAARLFIEWLKNGGPPSGAPPPK-NH ₂

Compound 279, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGKPPP-NH ₂

Compound 280.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGEPPPK-NH ₂

Compound 281, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSS(aib) APPPK-NH ₂

Compound 282, H (aib) EGTFTSDLSIALEEEAVRLFIEWLLAGGPSSGAPPPK (x20) -NH ₂

Compound 283, H (aib) EGTFTSDLSIALEEEAVRLFIAWLLAGGPSSGAPPPK (x20) -NH ₂

The peptide compound according to any one of the preceding aspects, wherein the peptide compound comprises only natural amino acids.

In one aspect the present invention relates to a pharmaceutical composition comprising a peptide compound as described above, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier or excipient.

In one aspect the invention relates to a method of treating or preventing the following diseases or conditions: impaired Glucose Tolerance (IGT), hyperglycemia, type 1 diabetes, diabetes type 2, obesity, metabolic syndrome, and neurodegenerative diseases, particularly for delaying or preventing disease progression in type 2 diabetes, delaying progression from impaired glucose tolerance to type 2 diabetes; delay progression from type 2 diabetes to insulin-requiring diabetes; treating metabolic syndrome, for regulating appetite, inducing satiety, reducing food intake, increasing energy expenditure, treating obesity or preventing overweight; preventing weight rebound after successful weight loss; treating a disease or condition associated with overweight or obesity; treating bulimia; treating overeating; treating dyslipidemia, atherosclerosis, hypertension, coronary heart disease, beta-blocker intoxication; non-alcoholic fatty liver disease (NAFLD) (which can be classified as Simple Fatty Liver (SFL), non-alcoholic steatohepatitis (NASH) and related cirrhosis); for inhibiting motility of the gastrointestinal tract for use in conjunction with gastrointestinal tract investigations using techniques such as X-ray, CT and NMR scanning; the method comprises administering to the patient an effective amount of a peptide compound of any of the preceding aspects, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition.

In one aspect the present invention relates to the use of a peptide compound of any one of the preceding aspects or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for use in lowering blood glucose or treating diabetes.

In one aspect the present invention relates to the use of a peptide compound of any one of the preceding aspects, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for use in weight loss.

In one aspect the present invention relates to the use of a peptide compound of any one of the preceding aspects, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for use in reducing blood lipids.

The invention carries out a series of structural modification on GLP-1 receptor agonist peptide derivatives, including selecting specific amino acid, or introducing new amino acid at the C terminal of the peptide, or substituting amino acid residue at the C terminal of the peptide, and linking a unique long-acting group to the polypeptide through cysteine residue side chain sulfhydryl at the C terminal of the polypeptide or side chain amino of lysine residue, thereby obtaining a brand new peptide compound. An unexpected technical effect is achieved.

Drawings

FIG. 1: compounds 4, 19, 38, 56, 99, 102, 103 and 253 of the present invention were tested for lowering blood glucose in db/db mice.

FIG. 2: test of the effect of compounds 82, 267, 273 of the invention on mouse body weight.

Detailed Description

The following definitions apply throughout the present invention unless otherwise indicated. Undefined terms may be understood according to conventional definitions defined within the industry.

"amino acid" refers to a molecule comprising both amino and carboxyl functional groups, the amino and carboxyl groups of an alpha-amino acid being attached to the same carbon atom (alpha carbon). The alpha carbon may additionally have 1-2 organic substituents. Amino acids comprise both L and D isomers and racemic mixtures. Unless otherwise specified, amino acid residues in the polypeptide sequences of the present invention are all L isomers, i.e., L-amino acids, and D-amino acids are indicated by the lowercase "D" before the amino acid name or abbreviation, e.g., dK.

The amino acid sequences of the present invention contain the conventional single or three letter codes for naturally occurring amino acids, as well as the commonly accepted three letter codes for other amino acids, such as Tic (1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid), Aib (α -aminoisobutyric acid), or GABA (γ -aminobutyric acid). Common abbreviated codes for molecular structures include:

the hGlu is homoglutamic acid;

a-hGlu is-HNCH (CO-) CH ₂ CH2CH ₂ The L isomer of COOH;

delta-hGlu is the L isomer of-HNCH (COOH) CH2CH2CH2 CO-;

alpha-Glu is-HNCH (CO-) CH ₂ CH ₂ The L isomer of COOH;

Gamma-Glu or gGlu is-HNCH (COOH) CH ₂ CH ₂ The L isomer of CO-;

alpha-Asp being-HNCH (CO-) CH ₂ The L isomer of COOH;

beta-Asp being-HNCH (COOH) CH ₂ The L isomer of CO-;

beta-Ala is-HN-CH ₂ -CH ₂ -COOH；

PEG2 is 2- (2- (2-aminoethoxy) ethoxy) acetic acid (CAS No. 134978-97-5).

The amino acid composition of the polypeptides of the invention may be varied without substantially affecting their biological activity. For example, a polypeptide sequence may comprise one or more conservative amino acid substitutions. Conservative amino acid substitutions are those in which one amino acid residue is replaced with another amino acid residue having a similar side chain. Amino acid residues are classified in the literature according to the nature of their side chains. Amino acid residues containing basic side chain include lysine, arginine, and histidine; amino acid residues comprising an acidic side chain and its amide side chain include aspartic acid, glutamic acid, asparagine, glutamine; small aliphatic, nonpolar or weakly polar side chain amino acid residues include glycine, alanine, threonine, serine, proline; the large aliphatic non-polar side chain amino acid residues comprise leucine, isoleucine and valine; aromatic amino acid residues include phenylalanine, tryptophan, tyrosine; the sulfur-containing side chain amino acid residues include cysteine and methionine.

In some embodiments, the derivative comprises a substituent comprising a lipophilic moiety and optionally a negatively charged moiety of 1-3, wherein one of the negatively charged moieties is distal to the lipophilic moiety. In some embodiments, the substituent is attached to the side chain of an amino acid at the C-terminus of the sequence. If the C-terminus of the sequence is lysine, it is linked to the epsilon amino group of the lysine residue.

As used herein, "expression vector" includes vectors capable of expressing DNA operably linked to regulatory sequences, such as promoter regions, capable of effecting the expression of such DNA fragments. Such additional fragments may include promoter and terminator sequences, and optionally may include one or more origins of replication, one or more selectable markers, enhancers, polyadenylation signals, and the like. Expression vectors are generally derived from plasmid or viral DNA, or may contain elements of both. Thus, an expression vector refers to a recombinant DNA or RNA construct, such as a plasmid, phage, recombinant virus, or other vector, which when introduced into an appropriate host cell results in the expression of the cloned DNA. Suitable expression vectors are well known to those skilled in the art and include those which are replicable in eukaryotic and/or prokaryotic cells, as well as expression vectors which remain episomal or which integrate into the genome of the host cell. In one embodiment, i.e., when a compound comprises genetically encoded amino acid residues, the invention further provides nucleic acids (which may be DNA or RNA) encoding the compound, vectors comprising such nucleic acids, and host cells comprising such nucleic acids or expression vectors.

As used herein, the term "treating" includes inhibiting, slowing, stopping or reversing the progression or severity of an existing symptom or condition. Thus, treatment includes prophylaxis, treatment and/or cure. Prevention refers to prevention of the underlying disease and/or prevention of worsening of symptoms or disease progression.

As used herein, "therapeutic effect" means an effect resulting from treatment of an individual that alters, typically ameliorates or improves a symptom of a disease or condition, or cures the disease or condition.

As used herein, "therapeutically effective amount" or "therapeutically effective dose" refers to an amount of a substance, compound, material, or composition comprising a compound that is at least sufficient to produce a therapeutic effect upon administration to a subject. Thus, it is the amount necessary to prevent, cure, ameliorate, block, or partially block the symptoms of the disease or disorder.

As used herein, a "prophylactically effective amount" or a "prophylactically effective dose" refers to an amount of a substance, compound, material, or composition comprising a compound that will have the intended prophylactic effect when administered to a subject, e.g., to prevent or delay the onset or recurrence of a disease or symptom, to reduce the likelihood of onset or recurrence of a disease or symptom. A complete prophylactically effective dose need not occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations.

As used herein, the term "patient" refers to a mammal, such as a human.

Holst (Holst, j.j.p. physiol.rev.2007,87,1409) and Meier (Meier, j.j.nat.rev.endocrinol.2012,8,728) describe GLP-1 receptor agonists such as GLP-1, liraglutide and exendin-4.

Certain compounds of the present invention are generally effective over a wide dosage range. For example, the once weekly dosage may range from about 0.05 to about 30mg per person per week. Certain compounds of the invention may be administered daily. In addition, certain compounds of the present invention may be administered once per week.

It is understood that the therapeutic agents according to the embodiments will be administered with pharmaceutically acceptable suitable carriers, excipients, and other agents incorporated into the formulation to provide improved transfer, delivery, tolerance, and the like. A large number of suitable formulations can be found in pharmacopoeias known to all pharmaceutical chemists: remington's Pharmaceutical Sciences (15 th edition, Mack Publishing Company, Easton, Pa. (1975)), particularly among them Blaug, Seymour chapter 87. Such formulations include, for example, powders, pastes, ointments, gels, waxes, oils, lipids, lipid-containing (cationic or anionic) carriers (e.g., Lipofectin. TM.), DNA conjugates, anhydrous slurries, oil-in-water and water-in-oil emulsions, emulsion polyethylene glycols (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing polyethylene glycols. Any of the foregoing mixtures may be suitable for use in the treatment or therapy according to the present invention, provided that the active ingredients in the formulation are not inactivated by the formulation and the formulation is physiologically compatible and tolerates the route of administration.

As used herein, the term "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the latest edition of Remington's Pharmaceutical Sciences, which is a standard bibliography of the art, and is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, ringer's solution, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous carriers, such as immobilized oils, can also be used. The use of such media and agents for pharmaceutically active substances is well known in the art.

The formulations to be used for clinical in vivo administration must be sterile. This can be easily achieved by filtration through sterile filtration membranes.

The compounds of the present invention may be reacted with any of a variety of inorganic or organic acids to form pharmaceutically acceptable acid addition salts. Pharmaceutically acceptable salts and common methods for preparing them are well known in the art. See, e.g., Handbook of Pharmaceutical Salts: properties, Selection and use, second revision (Wiley-VCH, 2011); berge et al, "Pharmaceutical Salts", Journal of Pharmaceutical Sciences, Vol.66, No.1, month 1 1977. Common pharmaceutically acceptable salts include trifluoroacetate, acetate, citrate, hydrochloride and the like.

The pharmaceutical compositions of the embodiments are formulated to be compatible with their intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions for parenteral, intradermal, or subcutaneous administration may include the following components: sterile diluents for injection such as water, saline solutions, fixed oils, polyethylene glycols, glycerin, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol, methyl paraben, phenol or m-cresol; antioxidants, such as ascorbic acid or sodium bisulfite; chelating agents, such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for adjusting the osmotic pressure, such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be packaged in ampoules, vials, disposable syringes, glass or plastic multi-dose vials or injection pens. The injection pen mainly has two types, one type is a disposable pre-filling pen, medicine is filled in the pen, a medicine pen core does not need to be replaced, and the pen can be thrown away after being used; the other type is a more commonly used durable injection pen which consists of an injection pen and a medicine pen core, and the pen core can be continuously used after being replaced.

Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (herein water-soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. For intravenous administration, suitable carriers include saline, bacteriostatic water, Cremophor ELTM (BASF, Parsippany, n.j.) or Phosphate Buffered Saline (PBS). In all cases, the compositions must be sterile and fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be resistant to the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycols, and the like), and suitable mixtures thereof. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, m-cresol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by incorporating a compound of the invention in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating a compound of the invention into a sterile vehicle which contains a dispersing medium and those other ingredients necessary as set forth above. In the case of sterile powders for the preparation of sterile injectable solutions, the preparation methods are vacuum drying and freeze-drying of the powders obtained containing the active ingredient in admixture with any additional desired ingredient resulting from sterile filtered solutions of such ingredients as previously described.

For administration by inhalation, the compounds are delivered in the form of an aerosol spray from a pressurized container or dispenser or a nebulizer containing a suitable propellant, e.g., a gas such as carbon dioxide.

Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, one or more of the compounds of the present invention may be formulated as ointments, creams, gels, or creams as generally known in the art.

The compounds may also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter or other glycerides) or retention enemas for rectal delivery.

In one embodiment, the compounds of the invention may be prepared with carriers that prevent their rapid elimination by the body, such as sustained/controlled release formulations, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers may be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparing such formulations will be apparent to those skilled in the art.

For example, these active ingredients may be encapsulated in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization methods, such as hydroxymethylcellulose or gelatin microcapsules and poly (methylmethacylate) microcapsules, respectively, in colloidal delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules) or macroemulsions.

Can be prepared into sustained release preparation. Examples of suitable sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the compound of the invention, which matrices are in the form of shaped articles, e.g. films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (e.g., poly (2-hydroxyethyl-methyl propionate), or poly (vinyl alcohol)), polylactide (U.S. Pat. No.3,773,919), copolymers of L-glutamic acid and γ -ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as LUPRON DEPOTTM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D- (-) -3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid are capable of releasing molecules for over 100 days, some hydrogels release proteins for shorter periods of time. Polylactic acid (PLA) and poly (lactic-co-glycolic acid) (PLGA) are hot spots studied in recent years. In addition, albumin microspheres, chitosan microspheres, gelatin microspheres, and the like are also available.

Liposomal suspensions may also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example as described in U.S. Pat. No.4,522,811.

It is particularly advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. As used herein, dosage unit form refers to physically discrete units suitable as unit doses for the subject to be treated; each unit containing a predetermined amount of one or more of the compounds of the invention calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specifications for the dosage unit form of the embodiments are indicated by and directly dependent on: the unique characteristics of the compounds of the present invention and the specific therapeutic effects to be achieved, and limitations inherent in the art of formulation of such compounds of the present invention for the treatment of individuals.

The pharmaceutical composition may be placed in a container, package, or dispenser with instructions for administration.

The present invention provides a method for treating type 2 diabetes in a patient comprising administering to a patient in need of such treatment an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof. The present invention also provides a method for treating type 2 diabetes in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof, wherein the administration is subcutaneous. The present invention also provides a method of treating type 2 diabetes in a patient, comprising administering to a patient in need of such treatment an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof, and administering simultaneously, separately, or sequentially an effective amount of one or more other active ingredients. In one embodiment, the other active ingredient or ingredients are currently available oral glucose lowering drugs from a class of drugs considered standard of care prior to administration (as determined by industry guidelines such as the American Diabetes Association).

The present invention also provides methods of treating or preventing the following diseases or conditions: impaired Glucose Tolerance (IGT), hyperglycemia, type 1 diabetes, type 2 diabetes, obesity, metabolic syndrome, and neurodegenerative diseases, particularly for delaying or preventing disease progression in type 2 diabetes, delaying progression from impaired glucose tolerance to type 2 diabetes; delay progression from type 2 diabetes to insulin-requiring diabetes; treating metabolic syndrome, for regulating appetite, inducing satiety, reducing food intake, increasing energy expenditure, treating obesity or preventing overweight; preventing weight rebound after successful weight loss; treating a disease or condition associated with overweight or obesity; treating bulimia; treating overeating; treating dyslipidemia, atherosclerosis, hypertension, coronary heart disease, beta-blocker intoxication; non-alcoholic fatty liver disease (NAFLD) (classified as simple fatty liver (sFL), non-alcoholic steatohepatitis (NASH) and related cirrhosis); for inhibiting motility of the gastrointestinal tract for use in conjunction with gastrointestinal tract investigations using techniques such as X-ray, CT and NMR scanning. The method comprises administering to a patient in need of such treatment an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt or solvate thereof, and administering simultaneously, separately or sequentially an effective amount of one or more other active ingredients.

Further preferred medical uses include the treatment or prevention of degenerative diseases, in particular neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, ataxia (e.g. spinocerebellar ataxia), Kennedy's disease, myotonic dystrophy, Lewy body dementia, multiple-system atrophy, amyotrophic lateral sclerosis, Primary lateral sclerosis, spinal muscular atrophy, prion-related diseases (e.g. Creutzfeldt-Jacob disease), multiple sclerosis, capillary amplification, Bettem disease (Batten disease), corticobasal degeneration, subacute degeneration, Sarkosis, and Tachthy tabes disease, Toxic encephalopathy, infant Refsum disease (inflanum disease), Refsum disease, neuroacanthocytosis, Niemann-Pick disease, Lyme disease (Lyme disease), Machado Joseph disease (Machado-Joseph disease), Sandhoff disease (Sandhoff disease), snow-ducle syndrome (she-Drager syndrome), hedgehog rocking syndrome (wbbldy hedgehog syndrome), prolycosis (proteopathsis), brain B-cerebrovascular amyloid, retinal ganglionic degeneration in glaucoma, nucleoproteopathy (synephathritis), tauopathy (tauopathy), senile temporal lobar degeneration (FTLD), dementia, caudal syndrome, hereditary cerebral hemorrhage with amyloidosis, Alexander disease (Alexander disease), amyotrophic lateral sclerosis (amyothrix), amyotrophic lateral degeneration (amyloid system), senile dementia (senile dementia), senile dementia, cardiac familial disease, amyloidosis, neurolysis, and amyloidosis, Peroneal muscular dystrophy (serpinopathies), AL (light chain) amyloidosis (primary systemic amyloidosis), AH (heavy chain) amyloidosis, AA (secondary) amyloidosis, intra-aortic amyloidosis (aortical medial amyloidosis), ApoAI amyloidosis, ApoAII amyloidosis, ApoAIV amyloidosis, finnish-type Familial Amyloidosis (FAF), lysozyme amyloidosis, fibrinogen amyloidosis, dialysis amyloidosis, inclusion body myositis/myopathy, cataracts, retinitis pigmentosa with rhodopsin mutations, medullary thyroid carcinoma, cardiac atrial amyloidosis, pituitary prolactinoma, Hereditary latticed corneal dystrophy (Hereditary interstitial amyloidosis), cutaneous licheniform amyloidosis, malorosomes (malloromy bodies), corneal lactoferrin amyloidosis, alveolar proteinosis (pulmonary amyloid deposition and pulmonary amyloid disease), Odontogenic (Pindborg) tumor amyloid, cystic fibrosis, sickle cell disease or critical myopathy (CIM). Further medical uses include the treatment of bone-related disorders, such as osteoporosis or osteoarthritis, where an increase in bone formation and a decrease in bone resorption (bone resorption) may be beneficial.

Abbreviations

Protecting groups:

aloc or AOC, allyloxycarbonyl: an allyloxycarbonyl group; bom, benzyloxymethylethyl: a benzyloxymethyl group; 2-Br-Z, 2-bromobenzyloxycarbonyl: 2-bromobenzyloxycarbonyl; tBu, t-butyl: a tertiary butyl group; bz, benzyl: a benzoyl group; bzl, benzyl: a benzyl group; boc, tert-butoxycarbnyl: a tert-butoxycarbonyl group; CHO, formyl: a formyl group; cHx, cyclohexyl: a cyclohexyl group; cbz or Z, benzyloxycarbonyl: a benzyloxycarbonyl group; 2-C1-Z, 2-chlorobenzoyloxy: 2-chlorobenzyloxycarbonyl; fm, 9-fluoroxylmethyl: 9-fluorenylmethyl; fmoc, 9-fluoroxylmethylcarbonyl: 9-fluorenylmethoxycarbonyl; mtt, 4-methylitrityl: 4-methyltriphenyl; pmc, (2, 2, 5, 7, 8-pentamethyl-6-sulfophenyl: 2, 2, 5, 7, 8-pentamethyl-6-hydroxychroman; Tos, 4-tolenesulphoryl: p-toluenesulfonyl; Trt, triphenylmethyl: trityl; Xan, xanthyl: xanthyl, oxa (hetero) anthryl.

Reagents and solvents:

ACN, acetonitrile: acetonitrile; BOP, benzotriazole-1-yloxytris (dimethylimine) phosphonium hexafluoro phosphate: benzotriazole-1-tris (trimethylamino) -hexafluorophosphate (a kat condensation agent); DCC, N' -dicyclohexylcarbodiimides: dicyclohexylcarbodiimide; DCM: dichloromethane; DEPBT, 3- (Diethoxyphosphinoyloxy) -1, 2, 3-benzotriazin-4(3H) -one: 3- (diethoxy-orthoacyloxy) -1, 2, 3-benzotriazin-4-one; DIC, N' -diisopropopylcarbodiimide: n, N' -diisopropylcarbodiimide; DIPEA (or DIEA), diisopyrophylamide: diisopropylethylamine; DMF: n, N-dimethylformamide; DMSO, DMSO: dimethyl sulfoxide; EDC or EDCI, 1-ethyl-3- (3-methylenepropyl) carbodiimide hydrochloride: 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride; EtOAc: ethyl acetate; HATU, 1- [ bis (methyleneamino) methyl ] -1H-1, 2, 3-triazolo [4, 5-b ] pyridine 3-oxide hexafluorophosphate: 1- [ bis (dimethylamino) methylene ] -1H-1, 2, 3-triazolo [4, 5-b ] pyridinium 3-oxide hexafluorophosphate; HBTU, O- (1H-benzotriazol-1-yl) -N, N' -tetramethyluronium hexafluorophosphate: benzotriazole-N, N, N ', N' -tetramethyluronium hexafluorophosphate; HOAT, 1-Hydroxy-7-azabenzotriazole: 1-hydroxy-7-azabenzotriazole; HOBT, 1-hydroxybenzotriazole: 1-hydroxy-benzo-triazole; Cl-HOBT: 6-chloro-1-hydroxy-benzo-triazole; NMM, N-methylorganophosphine: n-methylmorpholine; NMP, N-methylpyrrolidinone: n-methyl pyrrolidone; su, succinimide: a succinimide; TBTU, 2- (1H-Benzotriazole-1-y1) -1, 1, 3, 3-tetramethylammonium tetrafluoroborate: O-benzotriazole-N, N' -tetramethyluronium tetrafluoroborate; TEA, triethylamine: triethylamine; TFA, trifluoroacetic acid; TIS, trisisopystilcane: triisopropylsilane; TMP, 2, 2, 6, 6-Tetramethylpiperidine: 2.2.6.6-tetramethylpiperidine.

Chemical synthesis method of polypeptide

Solid Phase chemical synthesis of polypeptides is a well-developed methodology, and can be found in, for example, R.C. Sheppard, Solid Phase Peptide synthesis.A Practical Approach, Oxford-IRL Press, New York, 1989.

The linear polypeptides were synthesized using Boc solid phase polypeptide synthesis or Fmoc solid phase polypeptide synthesis. If Fmoc chemistry is used to synthesize a polypeptide with a carboxyl group at the C-terminus, Wang resin is typically used; the peptide having an amide at the C-terminus is usually selected from Rink amide resins (including RinkAmide-AM resin, RinkAmide-MBHA resin, etc.). If Boc chemistry is used to synthesize polypeptides with carboxyl groups at the c-terminus, Pam resin is generally chosen; the c-terminal amide polypeptide is usually selected from MBHA resin. Commonly used condensing and activating agents are DIC and HOBT, other optional peptide bond condensing agents include EDC, BOP, HBTU, DEPBT, TBTU and the like. According to the reaction difficulty, the amino acid can be used in an equivalent amount of 1.1-10 times, and the reaction time is 15 minutes-24 hours. The polypeptide can be synthesized manually or by using a polypeptide solid phase synthesizer.

The Fmoc protecting group was removed with 20% piperidine/DMF. The Boc protecting group was removed with TFA. The peptide bond condensation reaction was monitored with Ninhydrin (ninhydratin, 2, 2-dihydroindoline-1, 3-dione) reagent.

Solid phase synthesis may be performed using a resin preloaded with the C-terminal amino acid, or using a resin not loaded with the amino acid.

The loading of the first amino acid on the RinkAmide resin can be done by methods common in the art. One common method is briefly described as follows: the appropriate amount of resin was weighed, the Fmoc protecting group was removed in a solid phase synthesis tube with 20% piperidine/DMF (15mL/g resin, 30 min X2), and the resin was washed with DMF. Fmoc amino acid, HATU, HOAT and NMM are weighed, the equivalent of the Fmoc amino acid is 5 times of the resin amino group, the HATU, the HOAT and the NMM are 10 times of the resin amino group, DMF is added, and the mixture is uniformly mixed and transferred into a solid phase synthesis tube. After overnight reaction, the resin was washed with DMF. 1: 1 acetic anhydride/pyridine (v/v) was added to the solid phase synthesis tube, and after 30 minutes the tube was evacuated and the resin was washed with DMF. The first amino acid load is complete.

When Fmoc solid phase peptide synthesis is used, the commonly used amino acids and protecting groups are as follows:

Fmoc-Cys(Trt)-OH、Fmoc-Asp(OtBu)-OH、Fmoc-Glu(OtBu)-OH、Fmoc-His(Trt)-OH、Fmoc-Lys(Boc)-OH、Fmoc- Asn(Trt)-OH、Fmoc-G1n(Trt)-OH、Fmoc-Arg(Pmc)-OH、Fmoc-Ser(tBu)-OH、Fmoc-Thr(tBu)-OH、Fmoc-Trp(Boc)-OH、 Fmoc-Tyr(tBu)-OH

appropriately protected building blocks were used during the synthesis, such as the standard amino acids mentioned above, Fmoc-8-amino-3, 6-dioxaoctanoic acid (CAs No.166108-71-0), Fmoc-Glu-OtBu (CAS No. 84793-07-7). The introduction of the fatty acid moiety can be achieved using a structural unit such as, but not limited to, octadecanedioic acid mono-tert-butyl ester. After each coupling step, the unreacted peptide intermediate may be capped with acetic anhydride (10 equivalents) and an excess of collidine (20 equivalents).

After solid phase Fmoc chemistry to synthesize polypeptides, the commonly used cleavage reagent is TFA. The dry resin was placed in a shake flask and the appropriate amount of a mixture containing 90: 4: 2(v/v) trifluoroacetic acid: triisopropylsilane: 1, 2-ethanedithiol: water: the cutting solution (10-25mL/g resin) of thiobenzol was covered with a cap and subjected to intermittent rotary shaking at room temperature. After 2 hours the resin was filtered off with suction, the resin was washed 2-3 times with fresh TFA, the filtrates were combined and 8-10 times the volume of ethyl acetate was added dropwise. And finally, centrifugally collecting the precipitated crude polypeptide.

When using Boc solid phase polypeptide synthesis, the amino acids and protecting groups commonly used are as follows: Boc-Cys (4-MeBzl) -OH, Boc-Asp (OcHx) -OH, Boc-G1 u (OcHx) -OH, Boc-His (Bom) -OH, Boc-Lys (2-Cl-Z) -OH, Boc-Asn (Xan) -OH, Boc-Arg (tos) -OH, Boc-Ser (Bzl) -OH, Boc-Thr (Bzl) -OH, Boc-Trp (CHO) -OH and Boc-Tyr (2-Br-Z) -OH

If the side chain amino group of lysine is used for the synthesis of lactam or acylation reaction, the side chain amino group of lysine may be allyloxycarbonyl (a 1) _o c) Protection or Fmoc protection. If the side chain carboxyl group of aspartic acid or glutamic acid is used for lactam synthesis or acylation, the carboxyl group should be converted to allyl ester or 9-fluorenylmethyl protection, such as Boc-Glu (OAllyl) -OH, Boc-Glu (Ofm) -OH.

After solid phase Boc chemical synthesis of polypeptides, PAM and MBHA resins are cleaved, usually with HF, and 5ml of HF per 0.1 mmol of resin is added, together with reagents such as p-cresol, p-mercaptophenol or anisole, and the mixture is stirred for 1 hour under ice bath conditions. After vacuum pumping to dry HF, polypeptide is precipitated by ethyl acetate, and the precipitate is collected by centrifugation, separated and purified by HPLC, and freeze-dried to obtain the final product.

Purification of

The crude peptide is dissolved in a suitable mixture of water and acetonitrile (e.g., water/acetonitrile (3: 1)) and purified by reverse phase preparative HPLC (e.g., AKTA purifier, Shimadzu LC-20AR, etc.), using columns of different packing and size, e.g., C8 or C18 semi-preparative or preparative columns, depending on the amount and polarity size of the crude peptide loaded. Buffer a was 0.1% TFA in water and buffer B was 0.1% TFA in acetonitrile. Elution was carried out by increasing the gradient of buffer B, and the relevant fraction (fraction) was examined by analytical HPLC. A ZORBAX 300SB-C18(4.6X250mm, 5. mu.M) column was used, buffer A being 0.1% TFA in water and buffer B being 0.1% TFA in acetonitrile. The flow rate was 1ml/min, and the detection was carried out at a wavelength of 210 nm. Fractions containing pure target peptide were pooled and lyophilized to give the peptide trifluoroacetate salt as a white solid. The product is stored in glass vials.

Preparation method

The compounds of the invention are linear peptides. Each amino acid can be coupled stepwise in the order of the polypeptide sequence from the C-terminus to the N-terminus to provide a polypeptide backbone. The process is as follows: first, an amino acid having an amino group protected by a blocking group is covalently bound to a solid support, and the amino protecting group of the first amino acid is removed, whereby the first amino acid is bound to the solid support. The carboxyl group of the second amino acid, whose amino group is blocked, is then activated and reacts with the amino group of the first amino acid, which has been bound to the solid support, to form a peptide bond, thus forming a dipeptide with a protecting group on the solid support. The above peptide bond formation reaction is repeated to extend the peptide chain from the C-terminus to the N-terminus until the desired peptide chain is formed. Finally, the protecting group is removed, and the covalent bond between the peptide chain and the solid phase carrier is hydrolyzed to obtain the synthesized peptide.

The partial compound of the invention is conjugated with a long-acting group or a modifying group through the side chain amino group or the sulfhydryl group of the amino acid of which the side chain contains the amino group or the sulfhydryl group. The synthetic routes and methods are illustrated by way of example for compound 102.

The synthesis of compound 102 comprises the following steps:

step A: Fmoc-Lys (PG) -OH and resin are coupled to obtain Fmoc-Lys (PG) -resin, PG is a protective group of a side chain amino group of lysine;

and B: Fmoc-Lys (PG) -resin is subjected to first step-by-step coupling of amino acid or amino acid derivatives to obtain a first peptide resin with a sequence shown as a main peptide chain of a compound 102;

and C: removing a side chain protecting group PG of Lys in a first peptide resin with a sequence shown as a main peptide chain of a compound 102, and gradually coupling 2- (2- (2-aminoethoxy) ethoxy) acetic acid, gamma-Glu and octadecanedioic acid through a second step to obtain a second peptide resin;

step D: the second peptide resin was cleaved, purified and lyophilized to give compound 102.

Preferably, the resin in step A is a RinkAmide resin (including Rink Amide-AM resin, Rink Amide-MBHA resin, etc.). Preferably, the side chain protecting group of Lys is aloc, Mmt, Mtt, Dde or ivDde.

Preferably, the reagents used for the coupling are selected from DIC + A, B + A + C or B + C, wherein A is selected from HOAt or HOBt, B is selected from EDC, HATU, BOP, PyBOP, PyAOP, HBTU, TBTU or DEPBT, and C is selected from DIPEA, TEA, NMM or TMP.

For example, the coupling agent used in the first stepwise coupling in step B and the second stepwise coupling in step C comprises a condensing agent and a reaction solvent, and the condensing agent may be a mixture of DIC and HOBt, a mixture of PyBOP, HOBt and DIEA, or a mixture of HATU, HOAt and DIEA, or a mixture of deptt and DIEA, or a mixture of HBTU and DIEA. The reaction solvent is one or more of DMF, DCM, NMP or DMSO.

In the first stepwise coupling in step B, Fmoc-Pro-OH, Fmoc-Ala-OH, Fmoc-Gly-OH, Fmoc-Ser (tBu) -OH, Fmoc-Pro-OH, Fmoc-Gly-OH, Fmoc-Ala-OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ile-OH, Fmoc-Phe-OH, Fmoc-Leu-OH, Fmoc-Arg (Pbf) -OH, Fmoc-Val-OH, Fmoc-Ala-OH, Fmoc-Glu (OtBu), Fmoc-Glu (OH, Boc-Gly-Ala-OH, Fmoc-Leu-Ala-OH, Fmoc-Glu (Boc-OH, Fmoc-Ala-OH, Fmoc-Pro-OH, Fmoc-OH, Boc-Ala-OH, Boc-Ala-OH, Fmoc-Pro-OH, Boc-OH, Fmoc-OH, Boc-Pro-OH, Boc-OH, C-Ala-OH, C-OH, Boc-OH, C-Ala-OH, C-OH, and C-OH, C-OH, and the like, Fmoc-Lys (Boc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Leu-OH, Fmoc-Ala-OH, Fmoc-Ile-OH, Fmoc-Ser (tBu) -OH, Fmoc-Leu-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Thr (tBu) -OH, Fmoc-Phe-OH, Fmoc-Thr (tBu) -OH, Fmoc-Gly-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Aib-OH and Boc-His (trt) -OH.

When PG is aloc, the reagent used for removing the protecting group in the step C is 1-20 equivalents of morpholine (or 1-20 equivalents of phenylsilane substituted for morpholine) and 0.05-3 equivalents of Pd (PPh) ₃ ) ₄ And (4) removing. Preferably, the aloc protecting group is replaced with 5-10 equivalents of morpholine (or 5-10 equivalents of phenylsilane) to 0.1-0.3 equivalent of Pd (PPh) ₃ ) ₄ And (4) removing. The deprotection reaction may be carried out twice, each for 10 to 30 minutes, preferably with CH ₂ Cl ₂ Is a solvent.

Another method for removing the Aloc protecting group is to use a catalytic amount of tetrakis (triphenylphosphine) palladium (0) and a 37: 2: 1 ratio of DCM, glacial acetic acid and NMM (15mL/g resin) and stir under argon at room temperature for 2 hours. After the reaction, each gram of resin was washed with 0.5% DIPEA/DMF (10mL), 0.5% sodium diethyldithiocarbamate/DMF (3X10mL), 1: 1 DCM: DMF (5X10 mL).

When PG is Dde or ivDde, the reagent used for removing the protecting group in step C is hydrazine hydrate/DMF mixed solution. A DMF solution of 2% (w/v) hydrazine hydrate (25mL/g resin) was prepared, the resin was added, after 5 minutes it was drained and the resin was washed with DMF. The procedure of deprotection with 2% hydrazine hydrate/DMF and washing with DMF was repeated 3 times.

When PG is Mmt or Mtt, the reagent used for deprotecting in step C is 1-2% TFA/DCM mixture.

In the second stepwise coupling in step C, Fmoc-8-amino-3, 6-dioxaoctanoic acid (CASNO.166108-71-0), Fmoc-Glu-OtBu (CAS No.84793-07-7) and mono-tert-butyl octadecanedioate HOOC- (CH2)1 were stepwise coupled according to the sequence of Compound 102 ₆ -COOtBu. The reagent used in the cleavage in step D comprises TFA, PhSMe, PhOMe, EDT and H ₂ One, two or more than two of O, TIS and PhOH. For example, the reagent used for the cleavage is a mixture of TFA, thioanisole and EDT, and the volume ratio of TFA, thioanisole and EDT is 90: 5: 3: 2. Preferably, the reagents used for cleavage are TFA, H ₂ Mixed liquor of O and TIS with the volume ratio of 95: 2.5.

The invention also includes novel intermediates and processes useful in the synthesis of the compounds of the invention or pharmaceutically acceptable salts thereof. The intermediates and compounds of the present invention can be prepared by a variety of methods known in the art. In particular, the method using chemical synthesis is exemplified in the following examples. The specific synthetic steps of each of the routes described may be combined in different ways to prepare the compounds of the invention or salts thereof. Reagents and starting materials are readily available to those of ordinary skill in the art.

Examples

The invention is further illustrated with reference to examples. These examples are in no way intended to limit the scope of the claimed invention. Those skilled in the art can implement and apply the techniques of the present invention by taking the contents of the present invention into consideration, appropriately modifying the process parameters, and making changes or appropriate changes and combinations to the methods and applications of the present invention. All such substitutions and modifications will be apparent to those skilled in the art and are intended to be included herein.

Amino acid raw materials, condensing reagents, etc. were purchased from gill biochemical (shanghai) ltd. Rink Amide resins were purchased from Comp Paper and Tianjin Nankai and science and technology Limited.

EXAMPLE 1 Synthesis of Compound 7

Preloaded medium-low loading Fmoc-Ser (tBu) -Rink Amide resin (e.g., 0.4mmole/g) was selected, the Fmoc protecting group was removed with 30% piperidine/DMF (2X10 min), and the resin was washed 3 times with DMF. Fmoc solid phase polypeptide synthesis was used. The amino acid (10 equivalents relative to the resin amino acid loading) was dissolved in DMF to make a 0.3M solution. HOBT and DIC (10 equivalents relative to the amino acid loading of the resin) are added into the solution, the mixed solution is shaken and mixed evenly, then the resin is added, and the coupling is carried out for 60 minutes at room temperature. The solution in the solid phase reaction tube was drained and the resin was washed 3 times with DMF. This completes the coupling of one synthesis unit. The same coupling method is adopted for each synthesis unit from C terminal to N terminal of the polypeptide, and the amino acid residues are synthesized by using the commonly used protecting groups for Fmoc solid phase synthesis or other protecting groups suitable for the sequence listed in the section of 'solid phase chemical synthesis method of polypeptide'.

After peptide chain synthesis the resin was washed with DCM and added with a solution containing 90: 4: 2(v/v) trifluoroacetic acid: triisopropylsilane: 1, 2-ethanedithiol: water: methylthiophenyl ether cleavage solution (10-25mL/g resin), shaking at room temperature for 2 hours, and precipitating with glacial ethyl ether. The crude peptide was dissolved in 0.1% TFA, 30% aqueous acetonitrile and passed through a preparative RP-HPLC, C8, 5. mu.M reverse phase column. Buffer a was 0.1% TFA in water and buffer B was 0.1% TFA in acetonitrile. Elution was performed with a stepwise ascending gradient of buffer B, and the correct fractions (fraction) were pooled and lyophilized at low temperature to give a white solid. The structure of the polypeptide was determined by mass spectrometry and amino acid sequencing. The compound of the present invention in which the C-terminal is serine can be synthesized by the method of example 1.

EXAMPLE 2 Synthesis of Compound 4

Preloaded low-load Fmoc-Lys (Aloc) -Rink Amide resin (e.g., 0.29mmole/g) was selected. Each synthetic unit of the polypeptide from C-terminus to N-terminus was coupled using the coupling method of example 1, and amino acid residues other than C-terminal lysine were protected using commonly used protecting groups for Fmoc solid phase synthesis as exemplified in the section "solid phase chemical Synthesis of polypeptide". After peptide chain synthesis, the C-terminal lysine side chain alkene propoxycarbonyl group can be removed by using tetrakis (triphenylphosphine) palladium (0) and a ratio of 37: 2: 1DCM, glacial acetic acid and NMM (15mL/g resin) were stirred under argon at room temperature for 2 hours. Tetrakis (triphenylphosphine) palladium (0) may be used in catalytic amounts up to 1 equivalent. After the reaction, each gram of resin was washed with 0.5% DIPEA/DMF (10mL), 0.5% sodium diethyldithiocarbamate/DMF (3X10mL), 1: 1 DCM: DMF (5X10 mL). Aloc protecting groups may also be provided by reacting 5-10 equivalents of morpholine (or 5-10 equivalents of phenylsilane) with 0.1-0.3 equivalent of Pd (PPh) ₃ ) ₄ And (4) removing. The protecting group removing reaction can be carried out twice, each time is 30 minutes, and CH is selected ₂ Cl ₂ Is a solvent. After removal of the side chain Aloc protecting group, the synthesis of this lysine side chain substituent uses the building blocks Fmoc-8-amino-3, 6-dioxaoctanoic acid (CAS No.166108-71-0), Fmoc-Glu-OtBu (CAS No.84793-07-7) and octadecanedioic acid mono-tert-butyl ester HOOC- (CH. RTM.) (CH. C.) ₂ ) ₁₆ -COOtBu. The amount of side-chain substituents per structural unit was 10 equivalents of the resin amino acid loading, and the coupling time per step was 4 hours. The remaining synthesis and procedure were analogous to example 1.

Another method is to select preloaded low-load Fmoc-Lys (ivDde) -Rink Amide resin. The main peptide chain was synthesized in the same manner as in the previous paragraph using Fmoc-Lys (Aloc) -Rinkamide resin. After the synthesis of the main peptide chain, the protecting group of the C-terminal lysine side chain ivDde is removed by 2% hydrazine hydrate/DMF. A2% (w/v) solution of hydrazine hydrate in DMF (25mL/g resin) was prepared, the resin was added, 5 minutes of the needle was removed and the resin was washed with DMF. The procedure of deprotection with 2% hydrazine hydrate/DMF and washing with DMF was repeated 3 times. The synthesis method of the lysine side chain substituent is the same as the side chain linking method of the Fmoc-Lys (Aloc) -Rink Amide resin of the previous section. The compounds of the present invention in which the C-terminus is lysine and the long-acting group is attached to the amino group of the side chain can be synthesized by the method of example 2.

EXAMPLE 3 Synthesis of Compound 20

Selecting preloaded Fmoc-Cys (Trt) -Rink Amide resin. The rest of the synthesis and procedure were similar to example 1. The compound of the present invention in which the C-terminal is cysteine can be synthesized by the method of example 3.

EXAMPLE 4 Synthesis of Compound 81

Selecting preloaded Fmoc-Ala-Rink Amide resin. The rest of the synthesis and procedure were similar to example 1. The compound of the present invention in which the C-terminal is alanine can be synthesized by the method of example 4.

EXAMPLE 5 Synthesis of Compound 115

Selecting preloaded Fmoc-Gly-Rink Amide resin. The rest of the synthesis and procedure were similar to example 1. The compound of the present invention in which the C-terminal is glycine can be synthesized by the method of example 5.

Table 1 lists the calculated and measured molecular weights of some of the compounds of the invention.

TABLE 1

The mass spectrum molecular weight and amino acid sequencing result prove that the polypeptide structure is correct.

Example 6

Inserting human GLP-1 receptor gene into pEGFP-N3, constructing eukaryotic expression vector pEGFP-GLP-1R, transferring into HEK293 cell, obtaining after G418 pressure screening

HEK293 cells stably expressing human GLP-1 receptor were cultured in DMEM (Invitrogen, catalog #11960077) supplemented with 10% FBS (GIBCO, catalog No. 10099141). On the day of the assay, cells were harvested by trypsin solution (0.05%; Invitrogen, Cat #25300-

647 anti-cAMP antibody (1: 100, LANCETM cAMP 384 kit, PerkinElmer, Cat # AD 0264). The serially diluted test samples were incubated for 1 hour at room temperature in OptiPlate-384, white (Perkin-Elmer, Cat # 6007290). Post incubation 12Of microliter

cAMP detection mix is added to each well. The microplate was covered with a TopSeal-A membrane (Perkin-Elmer Co.) and incubated at room temperature for 60 minutes. TR-FRET fluorescence was measured on EnVision (Ex: 340 nm, Em: 615 nm and 665 nm, Perkin-Elmer, Inc.) after incubation. The effective 50% concentration was calculated by using GraphPad Prism 5. The average value was calculated after at least three measurements of each compound. The results are shown in Table 2.

In vitro activity assay results indicate that all compounds are highly active agonists of the GLP-1 receptor.

TABLE 2

The compound was dissolved in physiological saline (pH 7.4) to prepare stock solution. The concentration of the compound in the stock solution is determined by a conventional method such as Bradford method or UV spectrophotometry. Before animal drug effect test, compound stock solution containing required dosage is measured according to dosage, and diluted with buffered physiological saline (PBS, pH 7.4) to prepare injection. A suitable injection volume for each animal is 5ml/kg body weight. The volume of the injection solution to be dispensed can be calculated.

All data from animal experiments will be entered into Excel documents and expressed as mean ± s.e.m., the differences between groups compared using the graphed Prism 6 software using One-way analysis of variance (ANOVA) Dunnett's method, the differences between groups using unpaired T-Test method, and P values less than 0.05 considered significant differences.

Example 7

The in vivo efficacy of the compounds of the invention can be determined in any suitable animal model known in the art as well as in clinical trials. db/db mice are a relatively suitable animal model for diabetes.

And (3) feeding db/db mice in an animal feeding room with strictly controlled environmental conditions, wherein the temperature and the humidity of the feeding room are maintained at 20-24 ℃ and 40-70%. The temperature and humidity of the rearing room were monitored in real time by a hygrothermograph and recorded twice daily (1 each in the morning and afternoon). The lighting of the animal housing room is controlled by an electronic timing light-on system, which is turned on 12 hours a day and turned off 12 hours a day (7: 00 on in the morning and 19: 00 off in the afternoon). During the experiment, animals were housed in individual cages and toys were provided to mice in each cage. During the experiment, the animals had free access to water. db/db male mice (8 weeks old) were acclimated to the test environment for one week. Three days prior to the trial (-3 days to-1 day) baseline blood glucose and body weight were recorded. Mice were randomly grouped based on three days of blood glucose and body weight, 8 per group. Mice were in a 10 am: 00 subcutaneous injections of saline (5ml/kg, control) or compounds 4, 19, 38, 56, 99, 102, 103 and 253(20nmol/kg) were collected at 0 hour before and 1, 2, 4, 8, 24, 36 and 48 hours after administration, and blood glucose was measured using a Rogowski-mobil glucometer and a kit. And (3) drawing a blood glucose curve by taking the time as an abscissa and blood glucose values at different time points as an ordinate, calculating an area under the curve (AUC), and comparing the time and the effect of the compound on reducing the blood glucose.

The results are shown in FIG. 1. Compounds 4, 19, 38, 56, 99, 102, 103 and 253 all significantly reduced blood glucose in type 2 diabetic mice, statistically significantly different from the control group. These compounds have potential as long-acting therapeutic agents for diabetes.

Example 8

The in vivo efficacy of the polypeptides of the invention may be determined in any suitable animal model known in the art. Diet-induced obesity (DIO) mice are a common animal model for obesity, insulin resistance, and hyperlipidemia.

The 5-week-old male C57BL/6 mice are raised in an animal raising room with strictly controlled environmental conditions, wherein the temperature and humidity of the raising room are maintained at 20-24 ℃ and 30-70%. The temperature and humidity of the breeding room are monitored in real time through a hygrothermograph, and the temperature and the humidity are recorded once in the morning and afternoon every day. The lighting of the animal rearing room is controlled by an electronic timing light-on system, and the light is turned on for 12 hours every day and turned off for 12 hours (6: 00 am and 18: 00 pm). During the experiment, animals are raised in a single cage. Animals were fed with high fat diet from 6 weeks of age (protein 26.2%, carbohydrate 26.3%, fat 36.9% by weight, and heat percentage 20%, and 60%, respectively). During the feeding process, the animals drink water freely. Diet-induced obese (DIO) mice were obtained by feeding mice on high-fat diet. Male DIO mice of 30 weeks of age and an average body weight of about 48 g were selected for the test. Animals were acclimated to grasping and subcutaneous injection for 1 week. And the weight and the food intake are continuously measured for 3 days before the experiment, the blood sugar of the animals is measured 1 day before the experiment, and the animals are divided into 8 animals in each group according to the blood sugar and the weight of the animals.

The control group was injected subcutaneously every 2 days during the experiment with PBS. The other 3 groups of animals were injected subcutaneously once every 2 days with polypeptides 82, 267 and 273 (45nmol/kg), respectively, for a total of 15 times. Animals were weighed on day 30. Body weight change (grams) day 30 body weight-starting body weight.

The results are shown in FIG. 2. Polypeptide compounds 82, 267 and 273 all reduced body weight in DIO mice with statistically significant differences from the control group. These compounds have potential as long-acting weight-loss drugs.

Sequence listing

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<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 16

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 17

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (40)..(40)

<400> 17

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 18

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 18

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 19

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 19

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 20

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 20

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 21

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 21

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 22

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 22

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 23

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 23

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 24

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 24

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 25

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 25

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 26

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 26

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 27

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 27

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 28

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 28

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 29

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 29

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 30

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 30

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 31

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 31

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 32

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 32

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 33

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 33

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 34

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 34

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 35

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (40)..(40)

<400> 35

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 36

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 36

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Cys

35 40

<210> 37

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 37

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 38

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 38

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 39

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 39

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 40

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 40

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 41

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 41

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 42

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (40)..(40)

<400> 42

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 43

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 43

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Cys

35 40

<210> 44

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 44

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 45

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 45

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 46

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 46

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 47

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 47

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 48

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 48

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 49

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (40)..(40)

<400> 49

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 50

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 50

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 51

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 51

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 52

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 52

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 53

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 53

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 54

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 54

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 55

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 55

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 56

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 56

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 57

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 57

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 58

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 58

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 59

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 59

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 60

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 60

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 61

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 61

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 62

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 62

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 63

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 63

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 64

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 64

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 65

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 65

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 66

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 66

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 67

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 67

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 68

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 68

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 69

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 69

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 70

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 70

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 71

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 71

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 72

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 72

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 73

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 73

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 74

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 74

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 75

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 75

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 76

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 76

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 77

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 77

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 78

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 78

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 79

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 79

His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 80

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 80

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 81

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 81

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 82

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<223> C-terminal lysine = modified lysine, lysine ([ (2- (2- (2-aminoethoxy) ethoxy) acetyl) 2] - [ Γ -glutamic acid ] - [ 19-carboxynonadecanoyl ])

<400> 82

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 83

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 83

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 84

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 84

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 85

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 85

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 86

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 86

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 87

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 87

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 88

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 88

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 89

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 89

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 90

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 90

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 91

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 91

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 92

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 92

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 93

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 93

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 94

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 94

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 95

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 95

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 96

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 96

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 97

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 97

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 98

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 98

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 99

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 99

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 100

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 100

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 101

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 101

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 102

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 102

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 103

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 103

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 104

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 104

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 105

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 105

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 106

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 106

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Cys

35 40

<210> 107

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 107

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 108

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 108

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 109

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 109

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 110

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 110

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 111

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 111

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Cys

35 40

<210> 112

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 112

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 113

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 113

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 114

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 114

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 115

<211> 31

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (31)..(31)

<223> amidation, C-terminal amide

<400> 115

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Arg Gly

20 25 30

<210> 116

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 116

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 117

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 117

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 118

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 118

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 119

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 119

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 120

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 120

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 121

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 121

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 122

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 122

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 123

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 123

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 124

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 124

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 125

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 125

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 126

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 126

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 127

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 127

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Ile Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 128

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 128

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 129

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 129

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 130

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 130

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 131

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 131

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 132

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 132

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Cys

35

<210> 133

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 133

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Cys

35 40

<210> 134

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 134

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 135

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 135

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 136

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 136

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 137

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 137

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 138

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 138

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 139

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 139

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 140

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 140

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 141

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 141

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 142

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 142

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 143

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 143

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 144

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 144

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 145

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 145

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Ile Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 146

<211> 40

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (40)..(40)

<223> amidation, C-terminal amide

<400> 146

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Ile Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser Lys

35 40

<210> 147

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 147

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 148

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 148

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 149

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 149

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 150

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 150

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 151

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 151

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 152

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 152

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 153

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 153

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 154

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 154

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 155

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 155

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 156

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 156

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 157

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 157

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 158

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 158

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser

<210> 159

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 159

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 160

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 160

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 161

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 161

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 162

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 162

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 163

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 163

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Ile Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 164

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 164

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 165

<211> 36

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (36)..(36)

<223> amidation, C-terminal amide

<400> 165

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro

35

<210> 166

<211> 37

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (37)..(37)

<223> amidation, C-terminal amide

<400> 166

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ser Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro

35

<210> 167

<211> 37

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (37)..(37)

<223> amidation, C-terminal amide

<400> 167

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro

35

<210> 168

<211> 36

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (36)..(36)

<223> amidation, C-terminal amide

<400> 168

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro

35

<210> 169

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 169

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Leu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 170

<211> 31

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (31)..(31)

<223> amidation, C-terminal amide

<400> 170

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Arg Gly

20 25 30

<210> 171

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 171

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Lys

35

<210> 172

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 172

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 173

<211> 31

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (31)..(31)

<223> amidation, C-terminal amide

<400> 173

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Arg Gly

20 25 30

<210> 174

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 174

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Ile Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 175

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 175

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 176

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 176

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 177

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 177

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Ala Trp Leu Ile Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 178

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 178

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 179

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 179

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 180

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 180

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 181

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 181

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Lys

35

<210> 182

<211> 37

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (37)..(37)

<223> amidation, C-terminal amide

<400> 182

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Lys

35

<210> 183

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 183

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 184

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 184

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 185

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 185

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 186

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 186

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 187

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 187

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 188

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 188

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 189

<211> 31

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (31)..(31)

<223> amidation, C-terminal amide

<400> 189

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Arg Gly

20 25 30

<210> 190

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 190

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 191

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 191

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 192

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 192

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 193

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 193

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 194

<211> 30

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (30)..(30)

<223> amidation, C-terminal amide

<400> 194

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly

20 25 30

<210> 195

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 195

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Lys

35

<210> 196

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 196

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Ala Trp Leu Val Lys Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 197

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 197

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 198

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 198

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 199

<211> 31

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (31)..(31)

<223> amidation, C-terminal amide

<400> 199

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Arg Gly

20 25 30

<210> 200

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 200

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 201

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 201

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 202

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 202

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 203

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 203

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser

<210> 204

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 204

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 205

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 205

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 206

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 206

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 207

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 207

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 208

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 208

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 209

<211> 36

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 209

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Lys

35

<210> 210

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 210

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 211

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 211

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 212

<211> 34

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (34)..(34)

<223> amidation, C-terminal amide

<400> 212

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly

<210> 213

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 213

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 214

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 214

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Lys

35

<210> 215

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 215

His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 216

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 216

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 217

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 217

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 218

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 218

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 219

<211> 37

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (37)..(37)

<223> amidation, C-terminal amide

<400> 219

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Lys

35

<210> 220

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 220

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 221

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 221

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 222

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 222

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 223

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 223

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 224

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 224

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Val Lys Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 225

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 225

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 226

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 226

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 227

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 227

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Lys Glu Phe Ile Ala Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 228

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 228

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Lys

35

<210> 229

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 229

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 230

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 230

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 231

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 231

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 232

<211> 30

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (30)..(30)

<223> amidation, C-terminal amide

<400> 232

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Glu Phe Val Glu Trp Leu Leu Ala Gly Gly

20 25 30

<210> 233

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 233

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 234

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 234

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 235

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 235

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 236

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 236

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 237

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 237

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 238

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 238

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Lys

35

<210> 239

<211> 34

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (34)..(34)

<223> amidation, C-terminal amide

<400> 239

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Lys Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly

<210> 240

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 240

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 241

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 241

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 242

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 242

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 243

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 243

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 244

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 244

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 245

<211> 37

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (37)..(37)

<223> amidation, C-terminal amide

<400> 245

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Lys

35

<210> 246

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 246

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 247

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 247

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 248

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 248

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 249

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 249

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 250

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 250

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 251

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 251

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 252

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 252

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 253

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 253

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 254

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 254

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 255

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 255

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 256

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 256

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 257

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 257

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 258

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 258

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 259

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 259

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 260

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 260

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 261

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 261

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Gln Asp Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 262

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 262

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 263

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 263

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Gln Asp Phe Val Asn Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 264

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 264

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 265

<211> 37

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (37)..(37)

<223> amidation, C-terminal amide

<400> 265

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Lys

35

<210> 266

<211> 35

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (35)..(35)

<223> amidation, C-terminal amide

<400> 266

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala

35

<210> 267

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 267

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 268

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 268

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Tyr Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 269

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 269

His Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 270

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 270

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Xaa Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 271

<211> 33

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (33)..(33)

<223> amidation, C-terminal amide

<400> 271

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser

<210> 272

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 272

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Tyr Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Lys

35

<210> 273

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 273

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Xaa Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 274

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 274

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu Lys

1 5 10 15

Glu Ala Val Gln Asp Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Ser

35

<210> 275

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 275

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 276

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 276

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ser Ala Leu Glu Lys

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 277

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 277

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 278

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 278

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Ala Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Pro

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 279

<211> 38

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (38)..(38)

<223> amidation, C-terminal amide

<400> 279

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Lys Pro Pro Pro

35

<210> 280

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 280

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Gly Glu Pro Pro Pro Lys

35

<210> 281

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (34)..(34)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<400> 281

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser

20 25 30

Ser Xaa Ala Pro Pro Pro Lys

35

<210> 282

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 282

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 283

<211> 39

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (39)..(39)

<223> amidation, C-terminal amide

<220>

<221> MOD_RES

<222> (39)..(39)

<400> 283

His Xaa Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Ala Leu Glu Glu

1 5 10 15

Glu Ala Val Arg Leu Phe Ile Ala Trp Leu Leu Ala Gly Gly Pro Ser

20 25 30

Ser Gly Ala Pro Pro Pro Lys

35

<210> 284

<211> 30

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (2)..(2)

<223> X = alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (10)..(10)

<223> X=Leu, Val, Tyr

<220>

<221> MOD_RES

<222> (12)..(12)

<223> X=Ile, Ser, Lys

<220>

<221> MOD_RES

<222> (13)..(13)

<223> X = Gln, Ala, Tyr, alpha-aminoisobutyric acid

<220>

<221> MOD_RES

<222> (16)..(16)

<223> X=Lys, Glu

<220>

<221> MOD_RES

<222> (19)..(19)

<223> X=Val, Ala

<220>

<221> MOD_RES

<222> (20)..(20)

<223> X=Lys, Gln, Arg

<220>

<221> MOD_RES

<222> (21)..(21)

<223> X=Leu, Glu, Asp

<220>

<221> MOD_RES

<222> (23)..(23)

<223> X=Ile, Val

<220>

<221> MOD_RES

<222> (24)..(24)

<223> X=Ala, Glu, Asn

<220>

<221> MOD_RES

<222> (27)..(27)

<223> X=Lys, Val, Ile, Leu

<220>

<221> MOD_RES

<222> (28)..(28)

<223> X=Asn, Ala, Lys

<220>

<221> MOD_RES

<222> (30)..(30)

<223> X = absent or GPSSGAPPP, GPPSGAPPP, GPSSGKPPP, GPSSGEPPP, GPSSaibAPPP, GPSSGAPP, GPSSGAP, GPSSGA, GPSSG, GPSS, GPS, GP, G, RG

<400> 284

His Xaa Glu Gly Thr Phe Thr Ser Asp Xaa Ser Xaa Xaa Leu Glu Xaa

1 5 10 15

Glu Ala Xaa Xaa Xaa Phe Xaa Xaa Trp Leu Xaa Xaa Gly Xaa

<210> 285

<211> 11

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 285

Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser Lys

1 5 10

<210> 286

<211> 11

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 286

Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser Cys

1 5 10

<210> 287

<211> 10

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 287

Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser

1 5 10

<210> 288

<211> 10

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 288

Gly Pro Ser Ser Gly Ala Pro Pro Pro Lys

1 5 10

<210> 289

<211> 10

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 289

Gly Pro Ser Ser Gly Ala Pro Pro Pro Cys

1 5 10

<210> 290

<211> 9

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 290

Gly Pro Ser Ser Gly Ala Pro Pro Pro

1 5

<210> 291

<211> 9

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 291

Gly Pro Pro Ser Gly Ala Pro Pro Pro

1 5

<210> 292

<211> 9

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 292

Gly Pro Ser Ser Gly Lys Pro Pro Pro

1 5

<210> 293

<211> 9

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 293

Gly Pro Ser Ser Gly Glu Pro Pro Pro

1 5

<210> 294

<211> 9

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<220>

<221> MOD_RES

<222> (5)..(5)

<223> X = alpha-aminoisobutyric acid

<400> 294

Gly Pro Ser Ser Xaa Ala Pro Pro Pro

1 5

<210> 295

<211> 8

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 295

Gly Pro Ser Ser Gly Ala Pro Pro

1 5

<210> 296

<211> 7

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 296

Gly Pro Ser Ser Gly Ala Pro

1 5

<210> 297

<211> 6

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 297

Gly Pro Ser Ser Gly Ala

1 5

<210> 298

<211> 5

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 298

Gly Pro Ser Ser Gly

1 5

<210> 299

<211> 4

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 299

Gly Pro Ser Ser

1

<210> 300

<211> 3

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 300

Gly Pro Ser

1

<210> 301

<211> 2

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 301

Gly Pro

1

<210> 302

<211> 2

<212> PRT

<213> Artificial Sequence (Artificial Sequence)

<220>

<223> synthetic protein

<400> 302

Arg Gly

1

Claims

1. A peptide compound having the formula (I) or a pharmaceutically acceptable salt or solvate thereof,

H-aib-E-G-T-F-T-S-D-X1-S-X12-X2-L-E-X4-E-A-X5-X6-X3-F-X7-X8-W-L-X9-X11-G-X10 (I)

optionally, one or two amino acids selected from S or amino or sulfhydryl containing side chain are added at C-terminal of X10, and carboxyl of C-terminal amino acid is optionally amidated to C-terminal amide, the amino acid has formula

Wherein the wavy line represents the point of attachment to an adjacent group, n1 is an integer from 1 to 7, and when II or III is a C-terminal amino acid, the carboxyl moiety thereof is COOH or CONH ₂ Preferably, the amino acid containing a side chain amino group is lysine, the amino acid containing a side chain thiol group is cysteine,

optionally, the amino acid containing a side chain amino group added at the C-terminus of X10 is modified at its side chain amino group with a long-acting group, preferably, the long-acting group has the structure of formula (IV):

O1-O2-O3-O4-O5-O6-O7-O8- (IV)，

wherein O1 represents a structure of formula (V) or (VI):

wherein the wavy line represents the point of attachment of an amino group to an adjacent group, O2-O3-O4-O5-O6-O7-O8-represents a linker, wherein each of O2 to O8 is independently represented by any one of the following amino acid residues or long chain structures: α -Glu, γ -Glu, α -Asp, β -Asp, α -hGlu, δ -hGlu, Gly, Ala, β -Ala, GABA or PEG2, or one or more of O2 to O8 is absent, provided that at least two of O2 to O8 are present, preferably at least one negatively charged moiety is present in O2 to O8.

2. A peptide compound according to claim 1, wherein O2-O3-O4-O5-O6-O7-O8-represents a linker γ Glu-PEG2- γ Glu-, γ Glu-PEG2-2 Xγ Glu-, γ Glu-PEG2-, γ Glu-2 XPEG 2-, γ Glu-3 XPEG 2-, γ Glu-PEG2- γ Glu-PEG 32-, γ Glu-2 XPEG 2- γ Glu-, γ Glu-2 XPEG 2-2 Xγ Glu-, 2Xγ Glu-PEG2-, 2Xγ Glu-PEG2- γ Glu-, 2Xγ Glu-PEG2- γ Glu-PEG2-, 2Xγ Glu-2 XPEG 2-, or a pharmaceutically acceptable salt or solvate thereof, 2 XGamma Glu-2 XPEG 2-Gamma Glu, 2 XGamma Glu-2 XPEG 2-2 XGamma Glu-.

3. The peptide compound according to claim 1 or 2, or a pharmaceutically acceptable salt or solvate thereof, wherein the C-terminally added side chain thiol-containing amino acid of X10 is modified at its side chain thiol group by a long-acting group of formula (IV) which is linked to one end of a linking group L via a michael reaction acceptor or a thiol-reactive group, preferably the other end of the linking group L is further covalently linked to the long-acting group of formula (IV) via an amino or carboxyl group, preferably the linking group L is selected from: -NH- (CH) ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -，-NH-(CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -NH-，-NH-(CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -CO-，-NH-(CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -NHCO-(CH ₂ ) _n8 -，-NH-(CH ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -NHCO-(CH ₂ ) _n8 -NH-, or any combination thereof, wherein n3, n4, n5, n6, n7, n8 are each integers from 0 to 10, more preferably, L is-NH-CH ₂ -(CH ₂ CH ₂ O) ₃ -(CH ₂ ) ₃ -NH-or-NH- (CH) ₂ ) _n5 -(CH ₂ CH ₂ O) _n6 -(CH ₂ ) _n7 -NHCO-(CH ₂ ) _n8 -；

Preferably, the lysine side chain amino conjugation depot is K (x18) having the structure of formula (VIII)

Preferably, the lysine side chain amino conjugation depot is K (x20) having the structure of formula (IX):

preferably, the cysteine side chain thiol-conjugated depot is C (x18) having the structure of formula (XIV):

preferably, the cysteine side chain thiol-conjugated depot is C (x20) having the structure of formula (XV):

4. the peptide compound according to any one of the preceding claims 1 to 3, or a pharmaceutically acceptable salt or solvate thereof, wherein said peptide compound is selected from the group consisting of:

compound 1, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 2.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 3.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 4.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 5.H(aib)EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 6.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPC (x18) -NH ₂

Compound 7.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPS-NH ₂

Compound 8.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPSK-NH ₂

Compound 9.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPSK (x18) -NH ₂

Compound 10.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPK-NH ₂

Compound 11.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPK (x18) -NH ₂

Compound 12, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLNGGPSSGAPPPC-NH ₂

Compound 13.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLINGGPSSGAPPPS-NH ₂

Compound 14.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLIAGGPSSGAPPPS-NH ₂

Compound 15.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 16.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 17.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPSK (x18) -NH ₂

Compound 18.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 19.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 20.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 21.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVNGGPSSGAPPPS-NH ₂

Compound 22.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVNGGPSSGAPPPK-NH ₂

Compound 23.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVAGGPSSGAPPPS-NH ₂

Compound 24.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVAGGPSSGAPPPSK-NH ₂

Compound 25.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVAGGPSSGAPPPK-NH ₂

Compound 26.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVKGGPSSGAPPPS-NH ₂

Compound 27.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPS-NH ₂

Compound 28.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPK-NH ₂

Compound 29, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPSK-NH ₂

Compound 30.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 31.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 32.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 33, H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 34.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 35.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPSK (x18) -NH ₂

Compound 36.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPSC-NH ₂

Compound 37.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 38.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 39.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 40.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 41.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 42.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPSK (x18) -NH ₂

Compound 43.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPSC-NH ₂

Compound 44.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 45.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 46, H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 47, H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 48.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 49.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPSK (x18) -NH ₂

Compound 50.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 51.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 52.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 53.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 54.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPSK-NH ₂

Compound 55, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 56.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 57.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPC-NH ₂

Compound 58.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGAPPPC (x18) -NH ₂

Compound 59.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 60.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 61.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 62.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 63.H (aib) EGTFTSDLSKALEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 64.H (aib) EGTFTSDLSKALEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 65.H (aib) EGTFTSDLSIALEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 66.H (aib) EGTFTSDLSIALEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 67, H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGAPPPS-NH2

Compound 68.H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 69, H (aib) EGTFTSDLSKQLEEEAVKEFIEWLKNGGPSSGAPPPS-NH ₂

Compound 70.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPS-NH ₂

Compound 71.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPSK-NH ₂

Compound 72.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPK-NH ₂

Compound 73.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 74.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLKNGGPSSGAPPPC-NH ₂

Compound 75.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKAGGPSSGAPPPS-NH ₂

Compound 76.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 77.H (aib) EGTFTSDYSKQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 78.H (aib) EGTFTSDYSIQLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 79.H (aib) EGTFTSDVSSYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 80.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 81, H (aib) EGTFTSDLSKYLEEEAVKLFIEWLKNGGPSSGA-NH ₂

Compound 82.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPK (x20) -NH ₂

Compound 83.H (aib) EGTFTSDLSKYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 84.H (aib) EGTFTSDLSKYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 85.H (aib) EGTFTSDLSKYLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 86.H (aib) EGTFTSDYSKQLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 87.H (aib) EGTFTSDYSKQLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 88.H (aib) EGTFTSDYSKQLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 89.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 90.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 91, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 92.H (aib) EGTFTSDYSIYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 93.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 94.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 95.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 96.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 97, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 98.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 99.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 100.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 101, H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 102, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPK(x18)-NH ₂

Compound 103, H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 104.H (aib) EGrFTSDLSI (aib) LEKEAVRLFIEWLLAGGPSSGAPPPC (x18) -NH ₂

Compound 105, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 106.H (aib) EGTFTSDLSIAALEKEAVRLFIEWLLAGGPSSGAPPPSC-NH ₂

Compound 107.H (aib) EGTFTSDLSIAALEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 108.H (aib) EGTFTSDLSIAALEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 109.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 110.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 111.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPSC-NH ₂

Compound 112, H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 113.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 114.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 115.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLVKGRG-NH ₂

Compound 116.H (aib) EGTFTSDLSIALEKEAVKLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 117.H (aib) EGTFTSDLSIALEKEAVKLFIEWILAGGPSSGAPPPC-NH ₂

Compound 118.H (aibEGTFTSDLSLALEKEVKOLFIEWILAGGPSGAPPPK (x18) -NH ₂

Compound 119.H (aibEGTFTSDLSI (aib) LEKEAVKLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 120.H (aib) EGTFTSDLSI(aib) LEKEAVKLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 121, H (aib) EGTFTSDLSI(aib) LEKEAVKLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 122, H (aib) EGTFTSDLSIQLEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 123.H (aib) EGTFTSDLSLALEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 124.H (aib) EGTFTSDLSI(aib) LEKEAVRLFVNWLLAGGPSSGAPPPC-NH ₂

Compound 125.H (aib) EGTFTSDLSI(aib) LEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 126.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 127.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPK (x18) -NH ₂

Compound 128.H (aib) EGTFTSDLSIALEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 129, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 130.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 131, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 132.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPC-NH ₂

Compound 133, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPSC-NH ₂

Compound 134, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 135, H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 136.H (aib) EGTFTSDLSKQLEKEAVRLFIEWLLAGGPSSGAPPPK (x18)

Compound 137.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 138.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPSK-NH ₂

Compound 139.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 140.H (aib) EGTFTSDYSKYLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 141, H (aib) EGTFTSDYSKYLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 142, H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 143.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 144.H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 145.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPK-NH ₂

Compound 146.H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPSK-NH ₂

Compound 147, H (aib) EGTFTSDYSIYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 148.H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 149, H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 150.H (aib) EGTFTSDLSKQLEEEAVRLFVNWLKNGGPSSGAPPPS-NH ₂

Compound 151, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 152.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 153, H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 154.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNGGPSSGAPPPK-NH ₂

Compound 155.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 156.H (aib) EGTFTSDYSYRYLEKEARLRLFIEWLAGLSSGAPPPK (x18) -NH ₂

Compound 157, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLKAGGPSSGAPPPS-NH ₂

Compound 158, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSS-NH ₂

Compound 159.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 160.H(aib)EGTFTSDLSKALEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 161, H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 162.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 163, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLIAGGPSSGAPPPS-NH ₂

Compound 164.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 165, H (aib) EGTFTSDLSKALEKEAVRLFIEWLKNGGPSSGAP-NH ₂

Compound 166.H (aib) EGTFTSDLSSYLEEEAVRLFIEWLKNGGPSSGAPP-NH ₂

Compound 167, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPP-NH ₂

Compound 168, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAP-NH ₂

Compound 169, H (aib) EGTFTSDLSKQLEEEAVKLFIAWLKNGGPSSGAPPPS-NH ₂

Compound 170, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLVKGRG-NH ₂

Compound 171, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPK-NH ₂

Compound 172.H (aib) EGTFTSDLSKALEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 173.H (aib) EGTFTSDLSIALEEEAVRLFIEWLVKGRG-NH ₂

Compound 174.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLIAGGPSSGAPPPS-NH ₂

Compound 175.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 176.H (aib) EGTFTSDLSKQLEEEAVKEFIAWLLAGGPSSGAPPPS-NH ₂

Compound 177, H (aib) EGTFTSDLSKYLEEEAVRLFIAWLIAGGPSSGAPPPS-NH ₂

Compound 178, H (aib) EGTFTSDLSKALEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 179.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 180.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 181.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 182.H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSSGAPK-NH ₂

Compound 183, H (aib) EGTFTSDLSKYLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 184, H (aib) EGTFTSDLSKALEEEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 185.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 186.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 187.H (aib) EGTFTSDLSIQLEKEAVRLFIAWLKNGGPSSGAPPPS-NH ₂

Compound 188.H (aib) EGTFTSDYSIQLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 189, H (aib) EGTFTSDLSIALEKEAVRLFIEWLVKGRG-NH ₂

Compound 190, H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 191, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 192.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGA-NH2

Compound 193.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 194, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGG-NH ₂

Compound 195, H (aib) EGTFTSDLSIQLEKEAVRLFIEWLKNGGPSSGAPPK-NH ₂

Compound 196, H (aib) EGTFTSDLSKQLEEEAVRLFIAWLVKGGPSSGAPPPS-NH ₂

Compound 197.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 198, H (aib) EGTFTSDLSIQLEEEAVKEFIAWLKNGGPSSGAPPPS-NH ₂

Compound 199.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLVKGRG-NH ₂

Compound 200.H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 201, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGA-NH ₂

Compound 202, H (aib) EGTFTSDLSKALEEEAVRLFIEWLVKGGPSSGAPPPS-NH ₂

Compound 203, H (aib) EGTFTSDLSKALEEEAVRLFIEWLKNGGPSS-NH ₂

Compound 204.H (aib) EGTFTSDLSIYLEEEAVRLFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 205.H (aib) EGTFTSDLSIALEKEAVKEFIAWLVKGGPSSGAPPPS-NH ₂

Compound 206, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 207, H (aib) EGTFTSDLSIQLEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 208.H (aib) EGTFTSDYSIQLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 209.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAK-NH ₂

Compound 210.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 211, H (aib) EGTFTSDYSIALEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 212, H (aib) EGTFTSDYSKYLEKEAVRLFIEWLLAGGPSSG-NH ₂

Compound 213, H (aib) EGTFTSDYSKYLEEEAVKEFIAWLKNGGPSSGAPPPS-NH ₂

Compound 214.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 215.H (aib) EGTFTSDVSSYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 216, H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 217, H (aib) EGTFTSDLSIYLEEEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 218, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 219.H (aib) EGTFTSDLSLALEKEAVRLFIEWLLAGGPSSGAPK-NH ₂

Compound 220.H (aib) EGTFTSDYSIYLEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 221, H (aib) EGTFTSDLSIALEKEAVKEFIAWLLAGGPSSGAPPPS-NH ₂

Compound 222, H (aib) EGTFTSDYSIYLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 223H (aib) EGTFTSDYSIYLEEEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 224.H (aib) EGTFTSDLSKALEEEAVRLFIEWLVKGGPSSGAPPPK-NH ₂

Compound 225.H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 226, H (aib) EGTFTSDLSK(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 227, H (aib) EGTFTSDYSIYLEEEAVKEFIAWLLAGGPSSGAPPPS-NH ₂

Compound 228, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 229, H (aib) EGTFTSDYSIALEKEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 230.H (aib) EGTFTSDLSIALEKEAVRLFVNWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 231, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 232.H (aib) EGTFTSDLSIALEKEAVKEFVEWLLAGG-NH ₂

Compound 233, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 234, H (aib) EGTFTSDLSIYLEEEAVRLFIEWLLAGGPSS-NH ₂

Compound 235, H (aib) EGTFTSDLSIYLEEEAVRLFVNWLLAGGPSSGAPPPS-NH ₂

Compound 236.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 237, H (aib) EGTFTSDYSKALEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 238.H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 239, H (aib) EGTFTSDLSIYLEKEAVKLFVNWLLAGGPSSG-NH ₂

Compound 240.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 241, H (aib) EGTFTSDYSIQLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 242H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 243, H (aib) EGTFTSDYSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 244.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKNNGGPSSGA-NH ₂

Compound 245.H (aib) EGTFTSDLSIQLEKEAVRLFIEWLLAGGPSSGAPK-NH ₂

Compound 246.H (aib) EGTFTSDYSIYLEKEAVRLFVNWLLAGGPSSGAPPPK-NH ₂

Compound 247.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 248, H (aib) EGTFTSDLSI(aib) LEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 249.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 250, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSSGA-NH ₂

Compound 251, H (aib) EGTFTSDLSIYLEEEAVRLFVNWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 252, H (aib) EGTFTSDLSK(aib) LEKEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 253, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 254, H (aib) EGTFTSDLSIYLEKEAVRLFVNWLKNGGPSSGAPPPS-NH ₂

Compound 255, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 256.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGAPPPK (x20) -NH ₂

Compound 257, H (aib) EGTFTSDLSIYLEKEAVRIFIEWLKNGGPSSGAPPPK (x18) -NH ₂

Compound 258, H (aib) EGTFTSDYSIYLEEEAVRLFIEWLLAGGPSSGAPPPS-NH ₂

Compound 259, H (aib) EGTFTSDLSKALEEEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 260.H (aib) EGTFTSDLSKYLEKEAVRLFVNWLKNGGPSSGAPPPS-NH ₂

Compound 261, H (aib) EGTFTSDLSIQLEKEAVQDFVNWLLAGGPSSGAPPPK-NH ₂

Compound 262.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 263.H (aib) EGTFTSDLSKQLEEEAVQDFVNWLKNGGPSSGAPPPS-NH ₂

Compound 264, H (aib) EGTFTSDLSK(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK (x18) -NH ₂

Compound 265.H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGAPK-NH ₂

Compound 266, H (aib) EGTFTSDLSIYLEKEAVRLFIEWLLAGGPSSGA-NH ₂

Compound 267, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSSGAPPPK (x20) -NH ₂

Compound 268.H (aib) EGTFTSDLSIYLEKEAVRLFVNWLLAGGPSS-NH ₂

Compound 269.H (aib) EGTFTSDYSK(aib) LEEEAVRLFIEWLKNGGPSSGAPPPS-NH ₂

Compound 270.H (aib) EGTFTSDLSK(aib) LEEEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 271, H (aib) EGTFTSDLSIALEKEAVRLFIEWLLAGGPSS-NH ₂

Compound 272.H (aib) EGTFTSDLSKYLEEEAVRLFIEWLLAGGPSSGAPPK-NH ₂

Compound 273.H (aib) EGTFTSDLSI(aib) LEKEAVRLFIEWLLAGGPSSGAPPPK (x20) -NH ₂

Compound 274.H (aib) EGTFTSDLSIQLEKEAVQDFVNWLLAGGPSSGAPPPS-NH ₂

Compound 275.H (aib) EGTFTSDLSIALEKEAVRLFIEWLKAGGPSSGAPPPK (x20) -NH ₂

Compound 276.H (aib) EGTFTSDLSSALEKEAVRLFIEWLLAGGPSSGAPPPK-NH ₂

Compound 277, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLLAGGPSSGAPPPK (x20) -NH ₂

Compound 278.H (aib) EGTFTSDLSKQLEEEAARLFIEWLKNGGPPSGAPPPK-NH ₂

Compound 279, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGKPPP-NH ₂

Compound 280.H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSSGEPPPK-NH ₂

Compound 281, H (aib) EGTFTSDLSKQLEEEAVRLFIEWLKNGGPSS(aib) APPPK-NH ₂

Compound 282, H (aib) EGTFTSDLSIALEEEAVRLFIEWLLAGGPSSGAPPPK (x20) -NH ₂

Compound 283, H (aib) EGTFTSDLSIALEEEAVRLFIAWLLAGGPSSGAPPPK (x20) -NH ₂ 。

5. A pharmaceutical composition comprising a peptide compound according to any one of the preceding claims 1 to 4, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier or excipient.

6. Use of a peptide compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition according to claim 5, in the manufacture of a medicament for the treatment or prevention of: impaired Glucose Tolerance (IGT), hyperglycemia, type 1 diabetes, type 2 diabetes, obesity, metabolic syndrome, and neurodegenerative diseases, particularly for delaying or preventing disease progression in type 2 diabetes, delaying progression from impaired glucose tolerance to type 2 diabetes; delaying progression from type 2 diabetes to insulin-requiring diabetes, treating metabolic syndrome, for regulating appetite, inducing satiety, reducing food intake, increasing energy expenditure, treating obesity or preventing overweight; preventing weight rebound after successful weight loss; treating a disease or condition associated with overweight or obesity; treating bulimia; treating overeating; treating dyslipidemia, atherosclerosis, hypertension, coronary heart disease, beta-blocker intoxication; non-alcoholic fatty liver disease (NAFLD) (which can be classified as Simple Fatty Liver (SFL), non-alcoholic steatohepatitis (NASH) and related cirrhosis); for inhibiting motility of the gastrointestinal tract; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, ataxia (e.g. spinocerebellar ataxia), Kennedy's disease, myotonic dystrophy, Lewy body dementia, multiple system atrophy, amyotrophic lateral sclerosis, primary lateral sclerosis, spinal muscular atrophy, prion-related diseases (e.g. Creutzfeldt-Jacob disease), multiple sclerosis, capillary dilation, Buton's disease, basal degeneration (corticobasal degeneration), spinal subacute combined degeneration, tabes, Sasa-Sachs disease, Sargashi disease, neuro encephalopathy, and Lewy brain disease, Neuroacanthocytosis, Niemann-Pick disease, Lyme disease, machadolescent josephsis, Sandhoff disease, snow-ducher syndrome, hedgehog rocking syndrome, promorbidity, cerebral beta-cerebral vascular amyloid, retinal ganglioneuropathy in glaucoma, nucleoprotein diseases (synucleinopathies), tauopathies (tauopathies), frontotemporal lobar degeneration (FTLD), dementia, Cadasil syndrome, hereditary cerebral hemorrhage with amyloidosis, Alexander disease (Alexander disease), fibonadothiatus (septopathies), familial amyloidosis, senile systemic amyloidosis (amyotropic), amyloidosis, systemic amyloidosis, and amyloidosis AH (heavy chain) amyloidosis, AA (secondary) amyloidosis, intra-aortic amyloidosis (aortic medial amyloidosis), ApoAI amyloidosis, ApoAII amyloidosis, ApoAIV amyloidosis, finnish-type Familial Amyloidosis (FAF), lysozyme amyloidosis, fibrinogen amyloidosis, dialysis amyloidosis, inclusion body myositis/myopathy, cataracts, retinitis pigmentosa with rhodopsin mutations, medullary thyroid carcinoma, cardiac atrial amyloidosis, pituitary prolactinoma, Hereditary latticed corneal dystrophy (heredary corneal amyloid angiopathy), cutaneous licheniform amyloidosis, malloy cavities, keratolactoferrin amyloidosis, alveolar amyloidosis (pulmonary alveolar hypoperfusion), odontogenic (Pindborg) tumor amyloidosis, cystic fibrosis, myopathic cell disease or critical illness (m) tumors, A bone-related disorder.

7. Use according to claim 6, wherein the use is for the manufacture of a medicament for weight loss.

8. Use of a peptide compound according to any one of the preceding claims 1 to 4, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition according to claim 5, for the manufacture of a medicament for lowering blood lipid, preferably for lowering a blood lipid component selected from the group consisting of: cholesterol, triglycerides, free fatty acids, low density lipoprotein cholesterol; preferably, low density lipoprotein cholesterol is reduced.

9. Use of a peptide compound according to any one of the preceding claims 1 to 4 or a pharmaceutically acceptable salt or solvate thereof or a pharmaceutical composition according to claim 5 for the manufacture of a medicament for lowering blood glucose or treating diabetes.

10. A process for the preparation of a peptidic compound according to any one of claims 1 to 4, wherein said preparation process is a process by chemical synthesis.