Polypeptide compounds and their use in the treatment of enteritis - Patents.com

Abstract

The present invention relates to a new polypeptide and its application. The polypeptide provided by the present invention has a short peptide chain and is absorbed faster and better. Experimental results show that the polypeptide provided by the present application has a clear alleviating effect on intestinal lumen expansion in efficacy tests of zebrafish inflammatory bowel disease model and rat inflammatory bowel disease model. The polypeptide provided by the present invention has a significant alleviating effect on colitis and can be used to manufacture drugs for treating colitis, especially ulcerative colitis.

Description

[Technical field]

[0001] The present invention relates to a novel polypeptide and its application. The polypeptide of the present invention has a remarkable effect in treating inflammatory bowel disease, particularly in treating ulcerative colitis. [Background technology]

[0002] Enteritis is an intestinal inflammatory reaction caused by various factors such as infection or immune damage caused by enteric bacteria, viruses, etc., radiation damage, dietary irritation, drug irritation, etc. Clinical symptoms mainly include fever, nausea, vomiting, abdominal pain, diarrhea, watery stool or mucous purulent stool, and some patients may also have tenesmus.

[0003] Enteritis can be divided into specific enteritis and non-specific enteritis according to the symptoms of inflammation. Specific enteritis also includes inflammatory bowel disease, necrotizing enteropathy and intestinal flora dysbiosis. Among them, the more common inflammatory bowel disease is idiopathic, non-infectious, chronic, persistent, recurrent, inflammatory bowel disease that affects the intestinal tract. Clinical symptoms include abdominal pain, diarrhea, purulent bloody stool, and also include fever, abdominal tumor, weight loss, malnutrition and other symptoms. Inflammatory bowel disease is a chronic and long-term disease, and requires long-term active treatment.

[0004] In general, specific enteritis has a clear cause, such as bacterial enteritis, pseudomembranous enteritis, viral enteritis, and radiation enteritis, while nonspecific enteritis has an unclear cause and is thought to be caused by immune system diseases such as ulcerative colitis and Crohn's disease. Inflammatory bowel disease also includes ulcerative colitis and Crohn's disease. Ulcerative colitis is a chronic nonspecific intestinal inflammatory disease of unknown cause, which occurs most commonly in young adults. Clinical symptoms include persistent or recurrent diarrhea, mucous purulent stools with abdominal pain, tenesmus, and systemic symptoms of various degrees. Extraintestinal symptoms such as skin, mucous membranes, joints, eyes, liver, and gallbladder may appear. Complications include toxic megacolon, intestinal perforation, massive lower gastrointestinal bleeding, intraepithelial neoplasia, and cancer. In China, accurate UC incidence data is lacking, and according to regional epidemiological surveys, the incidence of UC in China is 0.42-2.22 / 100,000. Although the incidence rate is still low compared to Western countries, it shows a clear increasing trend compared to 20 years ago. The lesions mainly affect the mucosa and submucosa of the colon, the range starts from the distal colon of the rectum, progresses retrogradely toward the proximal end, and may further affect the entire colon, and 5% may affect the terminal ileum, and are distributed continuously. The main clinical symptoms of ulcerative colitis are diarrhea, abdominal pain, and mucous purulent stool, the cause of which has not yet been elucidated and is currently thought to be related to infectious diseases, immune abnormalities, genetic and psychological factors. In addition, patients with enteritis generally have symptoms such as intestinal lumen expansion (also called intestinal tract expansion or intestinal tract expansion), in which inflammation destroys the regulatory mechanism of nerves and muscles that control the normal intestinal tract, and the pressure in the intestinal lumen causes the expansion of the intestinal lumen wall beyond its normal mobility. Or it is caused by excessive growth of microorganisms and the toxins produced by them, mucus exudation, etc. Relieving or inhibiting the expansion of the intestinal lumen is helpful in treating enteritis. Summary of the Invention [Problem to be solved by the invention]

[0005] Currently, the drugs commonly used to treat ulcerative colitis have certain preventive and therapeutic effects, but they still have disadvantages such as relatively slow absorption, relatively long treatment cycle, and unclear treatment effect. [Means for solving the problem]

[0006] In order to overcome the shortcomings and defects of the prior art, the objective of the present invention is to provide a new polypeptide compound and its application.The inventors of the present invention have found that the polypeptide compound of the present invention can effectively or significantly alleviate or inhibit the expansion of intestinal lumen, thereby playing a role in treating enteritis.

[0007] According to a first aspect, the present invention relates to a compound according to formula (I) or a physiologically acceptable salt thereof, wherein said compound of formula (I) is HX a -Z 1 -Z 2 -Z 3 -Z 4 -X b -OH(I), Where: Z 1 is Pro, Ala, Gly, D-Pro or is deleted, Z 2 is Val, Ala, D-Val, Ile or is deleted, Z 3 is Pro, Ala, Gly, D-Pro or is deleted, Z 4 is Gln, Ala, Glu, Ile, D-Gln or is deleted, As a condition, Z 1 , Z 2 , Z 3 and Z 4 Two or fewer of these are deleted. X a is a sequence containing 0 to 10 amino acid residues, X b is a sequence containing 0 to 9 amino acid residues.

[0008] In one embodiment, Z1 , Z 2 , Z 3 and Z 4 In one embodiment, two of Z 1 and Z 2 In one embodiment, Z 3 and Z 4 In one embodiment, Z 1 , Z 2 , Z 3 and Z 4 In one embodiment, one of Z 1 In one embodiment, Z 4 In one embodiment, Z 1 , Z 2 , Z 3 and Z 4 0 of them are deleted.

[0009] In one embodiment, Z 1 Pro, Z 2 Val, Z 3 Pro and Z 4 is Gln. 1 D-Pro, Z 2 Val, Z 3 Pro and Z 4 is Gln. 1 Pro, Z 2 Val, Z 3 Ala and Z 4 is Gln. 1 Pro, Z 2 Ile, Z 3 Pro and Z 4 is Gln. 1 Pro, Z 2 Val, Z 3 Pro and Z 4 In one embodiment, Z 1 Pro, Z 2 Ala, Z 3 Pro and Z 4 is Gln. 1 Gly, Z2 Val, Z 3 Pro and Z 4 is Gln. 1 Pro, Z 2 Val, Z 3 Gly and Z 4 is Gln. 1 Ala, Z 2 Val, Z 3 Pro and Z 4 is Gln. 1 Pro, Z 2 Val, Z 3 Pro and Z 4 is Glu. In one embodiment, Z 1 Pro, Z 2 Val, Z 3 D-Pro and Z 4 is Gln. 1 Pro, Z 2 Val, Z 3 Pro and Z 4 is D-Gln.

[0010] In one embodiment, X a isX a10 -X a9 -X a8 -X a7 -X a6 -X a5 -X a4 -X a3 -X a2 -X a1 -*, where * is Z 1 -Z 2 -Z 3 -Z 4 represents the position of coupling to X a10 is Gly or is deleted, X a9 is Gly, Pro, Ser or is deleted, X a8 is Pro, Glu, Ser or is deleted, X a7is Arg, Glu, Thr, Ser or is deleted, X a6 is Lys, Thr, Ala, Asp, Glu, Arg, Ser or is deleted, X a5 is Asp, Ala, Val, Arg, Phe, Ile, Pro, Lys, Glu or is deleted, X a4 is Val, Phe, Pro, Pyro-Glu, Lys, Leu, Ile, Ala, Asp or is deleted, X a3 is Tyr, Leu, Pro, Asp, Arg, Glu, Lys, Tys, Val, Ile or is deleted, X a2 is D-Lys, Lys, Ala, Arg, Val, Glu, Tyr or is deleted, and X a1 is Glu, Ala, D-Glu, Tyr, Gln, Asp, Asn or is deleted.

[0011] In one embodiment, X a isX aa -X a2 -X a1 -*, where * is Z 1 -Z 2 -Z 3 -Z 4 represents the position of connection to X a2 -X a1 is Lys-Glu-*, Arg-Glu-*, Val-Tyr-*, Glu-Glu-*, Lys-Gln-*, Lys-D-Glu-* or Tyr-Glu-*, and X aa isX a10 -X a9 -X a8 -X a7 -X a6 -X a5 -X a4 -X a3 - where X a10 is Gly or deleted, and X a9 is Gly, Pro, Ser or deleted, and X a8 is Pro, Glu, Ser or deleted, and Xa7 is Arg, Glu, Thr, Ser or is deleted, and X a6 is Lys, Thr, Ala, Asp, Glu, Arg, Ser or is deleted, and X a5 is Asp, Ala, Val, Arg, Phe, Ile, Pro, Lys, Glu or is deleted, and X a4 is Val, Phe, Pro, Pyro-Glu, Lys, Leu, Ile, Ala, Asp or is deleted, and X a3 is Tyr, Leu, Pro, Asp, Arg, Glu, Lys, Tys, Val, Ile or is deleted. aa is Arg-Lys-Asp-Val-Tyr-, Gly-Pro-Glu-Thr-Ala-Phe-Leu-, Val-Pro-Pro-, Pyro-Glu-Leu-, Arg-Lys-Asp-, Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-, Ser-Ser-Glu-Asp-Ile-Lys-Glu-, Ser-Ser-Glu-Asp-Ile-Lys-, Val-Pro-Tys-, Pro-Ala-Tys-, Arg-Lys-Asp-Val-, Ser-Ser-Glu-Asp-Ile- or deleted, wherein the rightmost hyphen - is -X a2 -X a1 In one embodiment, X a isX aa -X a2 -X a1 -*, where * is Z 1 -Z 2 -Z 3 -Z 4 where X represents the position of the linkage to a2 -X a1 is Lys-Glu-*, and X aa is as defined above.

[0012] In one embodiment, X a isX a1 -*, where * is Z 1 -Z 2 -Z 3 -Z 4where X represents the position of the linkage to a1 is Glu, Ala, D-Glu, Asp, Asn or is deleted. In one embodiment, X a isX a2 -X a1 -*, where * is Z 1 -Z 2 -Z 3 -Z 4 where X represents the position of the linkage to a2 is Lys, and X a1 is Glu, D-Glu or Gln.

[0013] In one embodiment, X a are Glu-*, Ala-*, D-Glu-*, Asp-*, Asn-*, Lys-Glu-*, D-Lys-Glu-*, Ala-Glu-*, Lys-Gln-*, Lys-D-Glu-*, Lys-Ala-*, Arg-Lys-Asp-Val-Ty r-Lys-Glu-*, Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Glu-*, Val-Pro-Pro-Lys-Glu-*, Pyro-Glu-Leu-Lys-Glu-*, Arg-Lys-Asp-Val-Tyr-* , Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Lys-Glu-*, Ser-Ser-Glu-Asp-Ile-Lys-Glu-Lys-Glu-*, Ser-Ser-Glu-Asp-Ile-Lys-Glu-Glu-*, Val-Pro-Tys-Lys-Glu-*, Pro-Ala-Tys-Lys-Glu-*, Arg-Lys-Asp-Val-Tyr-Glu-*, Ser-Ser-Glu-Asp-Ile-Lys-Glu-* or deletion, wherein * is Z 1 -Z 2 -Z 3 -Z 4 Represents the position where the

[0014] In one embodiment, X b **-X b1 -X b2 -X b3 -X b4 -Xb5 -X b6 -X b7 -X b8 -X b9 where ** is Z 1 -Z 2 -Z 3 -Z 4 represents the position of coupling to X b1 is Ala, D-Ala or deleted, X b2 is Lys, Ala, D-Lys, Arg or is deleted, X b3 is Pro, Gly, D-Pro, Ser, Val, Ala or is deleted, X b4 is Arg, Ala, Ser, Pro, D-Arg or is deleted, X b5 is Lys, Ala, D-Lys, Glu, Tyr or is deleted, X b6 is Val, Asp, D-Val, Ala or is deleted, X b7 is Ala, D-Ala, Ile or is deleted, X b8 is Ala, D-Ala, Lys or is deleted, and X b9 is Gln, Ala, Glu, Asn, D-Gln or is deleted.

[0015] In one embodiment, X b **-X b1 -X b2 -X b3 -X b4 -X b5 -X b6 -X b7 -X b8 -X b9 where ** is Z 1 -Z 2 -Z 3 -Z 4 represents the position of coupling to X b1 is Ala or D-Ala, Xb2 is Lys, Ala or D-Lys, X b3 is Pro, Gly, or Ala, X b4 is Arg or D-Arg, X b5 is Lys or is deleted, X b6 is Val, D-Val, Ala or deleted, X b7 is Ala or deleted, X b8 is Ala or deleted, and X b9 is Gln, Asn, D-Gln or is deleted.

[0016] In one embodiment, X b **-X b1 -X b2 -X bb where ** is Z 1 -Z 2 -Z 3 -Z 4 represents the position of connection to X b1 -X b2 - is **-Ala-Lys-, **-Ala-Lys-, **-Ala-D-Lys-, **-Ala-Ala- or **-D-Ala-Lys-, X bb isX b3 -X b4 -X b5 -X b6 -X b7 -X b8 -X b9 where X b3 is Pro, Gly, D-Pro, Ser, Val, Ala or is deleted, and X b4 is Arg, Ala, Ser, Pro, D-Arg or deleted, and X b5 is Lys, Ala, D-Lys, Glu, Tyr or is deleted, and X b6 is Val, Asp, D-Val, Ala or is deleted, and X b7 is Ala, D-Ala, Ile or deleted, and X b8is Ala, D-Ala, Lys or is deleted, and X b9 is Gln, Ala, Glu, Asn, D-Gln or is deleted or X b3 is Pro, Gly, or Ala, and X b4 is Arg or D-Arg, and X b5 is Lys or deleted, and X b6 is Val, D-Val, Ala or deleted, and X b7 is Ala or deleted, and X b8 is Ala or deleted, and X b9 is Gln, Asn, D-Gln or is deleted. bbis Pro-Arg-Lys-Val, -Pro-Arg-Lys, -Pro-Arg, -Ala-Gln, -Ala-Ala, -Pro, -Lys-Val, -Val-Pro-Tyr, -Arg-Ly s, -Val-Ala, -Pro-Arg-Lys-Val-Ala, -Lys-Val-Ala-Ala-Gln, -Pro-Arg-Lys-Val-Ala-Ala-Gln, -Pro-Arg-L ys-Val-Ala-Ala-Gln, -Pro-Ala-Lys-Val-Ala-Ala-Gln, -Pro-Arg-Ala-Val-Ala-Ala-Gln, -Pro-Arg-Lys-Va l-Ala-Ala-Ala, -Gly-Arg-Lys-Val-Ala-Ala-Gln, -D-Pro-Arg-Lys-Val-Ala-Ala-Gln, -Pro-Arg-D-Lys-Val -Ala-Ala-Gln, -Pro-Arg-Lys-Val-D-Ala-Ala-Gln, -Pro-Arg-Lys-Val-Ala-D-Ala-Gln, -Ser-Ser-Glu-Asp -Ile-Lys-Glu, -Pro-Arg-Lys-Val-Ala-Ala-Asn, -Pro-Arg-Lys-Val-Ala-Ala-Gln, -Pro-Arg-Lys-D-Val-Al a-Ala-Gln, -Ala-Arg-Lys-Val-Ala-Ala-Gln, -Pro-Arg-Lys-Ala-Ala-Ala-Gln, -Pro-Arg-Lys-Val-Ala-Ala-Gln, -Pro-Arg-Lys-Val-Ala-Ala-Gln, -Pro-D-Arg-Lys-Val-Ala-Ala-Gln, -Pro-Arg-Lys-Val-Ala-Ala-D-Gln or deleted, wherein the leftmost hyphen - is X b1 -X b2 In one embodiment, X b **-X b1 -X b2 -X bb where ** is Z 1 -Z 2 -Z 3 -Z 4 represents the position of connection to X b1 -X b2 - is **-Ala-Lys-, and X bb is as defined above. In one embodiment, X b is **-Ala-.

[0017] In one embodiment, X b**-Ala-, **-Ala-Lys, **-Ala-D-Lys-, **-Ala-Ala-, **-D-Ala-Lys, **-Ala-Arg, **-Ala-Lys-Pro-Arg-Lys-Val, **-Ala-Lys-Pro-Arg-Lys, **-Ala-Lys-Pro-Arg, **-Val-Ala-Ala-Gln, **-Lys-Val-Ala-Ala, **-Ala-Lys-Pro, **-Pro-Arg-Lys-Val, **-Ala-Lys-Val-Pro-Tyr, **-Lys-P ro-Arg-Lys、**-Arg-Lys-Val-Ala、**-Ala-Lys-Pro-Arg-Lys-Val-Ala、**-Pro-Arg-Lys-Val-Ala-Ala-Gln、**-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln、**-Ala-Ala-Pro-Arg-Lys-Val-Ala-Ala-Gln、**-Ala-Lys-Pro-Ala-Lys-Val-Ala-Ala-Gln、**-Ala-Lys-Pro-Arg-Ala-Val-Ala-Ala-Gln、**-Ala-Lys-Pro-Arg-Ala-Val-Ala-Ala -Gln、**-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Ala、**-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln、**-Ala-Lys-D-Pro-Arg-Lys-Val-Ala-Ala-G ln、**-Ala-Lys-Pro-Arg-D-Lys-Val-Ala-Ala-Gln、**-Ala-Lys-Pro-Arg-Lys-Val-D-Ala-Ala-Gln、**-Ala-Lys-Pro-Arg-Lys-Val-Ala-D-Ala -Gln、**-Ala-Lys-Ser-Ser-Glu-Asp-Ile-Lys-Glu、**-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Asn、**-Ala-D-Lys-Pro-Arg-Lys-Val-Ala-Ala-G ln、**-Ala-Lys-Pro-Arg-Lys-D-Val-Ala-Ala-Gln、**-Ala-Lys-Ala-Arg-Lys-Val-Ala-Ala-Gln、**-Ala-Lys-Pro-Arg-Lys-Ala-Ala-Ala-Gln、**-D-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln, **-Ala-Lys-Pro-D-Arg-Lys-Val-Ala-Ala-Gln, **-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln, **-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-D-Gln or deletions, where ** is Z, 1 -Z 2 -Z 3 -Z 4 Represents the position where the

[0018] In one embodiment, Z 1 Pro, Z 2 Val, Z 3 Pro and Z 4 is Gln, and X a isX aa -X a2 -X a1 -*, where * is Z 1 -Z 2 -Z 3 -Z 4 where X represents the position of the linkage to a2 -X a1 Lys-Glu-* and X b **-X b1 -X b2 -X bb where ** is Z 1 -Z 2 -Z 3 -Z 4 represents the position of connection to X b1 -X b2 - is **-Ala-Lys-, where X aa and X bb is as defined above.

[0019] In one embodiment, the compound is Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 1), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys (compound 2), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (Compound 3), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 4), Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 5), Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 6), Lys-Glu-Pro-Val (Compound 7), Val-Ala-Ala-Gln (Compound 8), Glu-Pro-Val-Pro (Compound 9), Lys-Pro-Arg-Lys (Compound 10), Ala-Lys-Pro-Arg (Compound 11), Pro-Val-Pro-Gln (Compound 12), Val-Pro-Gln-Ala (Compound 13), Pro-Gln-Ala-Lys (Compound 14), Arg-Lys-Val-Ala (Compound 15),

[0020] Lys-Val-Ala-Ala (Compound 16), Gln-Ala-Lys-Pro (Compound 17), Pro-Arg-Lys-Val (Compound 18), Ala-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 19), Lys-Ala-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 20), Lys-Glu-Ala-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 21), Lys-Glu-Pro-Val-Ala-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 22), Lys-Glu-Pro-Val-Pro-Ala-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 23), Lys-Glu-Pro-Val-Pro-Gln-Ala-Ala-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 24), Lys-Glu-Pro-Ala-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 25), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Ala-Arg-Lys-Val-Ala-Ala-Gln (compound 26), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Ala-Lys-Val-Ala-Ala-Gln (compound 27), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Ala-Val-Ala-Ala-Gln (compound 28), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Ala-Ala-Ala-Gln (compound 29), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Ala (compound 30),

[0021] Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 31), Lys-Glu-Pro-Val-Gly-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 32), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (compound 33), Lys-Glu-Pro-Val-Gly-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (compound 34), Lys-Glu-Gly-Val-Gly-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (compound 35), Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (compound 36), Lys-Glu-Gly-Val-Gly-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 37), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys (Compound 38), Pro-Val-Pro-Gln-Ala (Compound 39), Pro-Val-Pro-Glu-Ala (Compound 40), Pro-Val-Pro-Ile-Ala (Compound 41), Pro-Val-Pro-Ala (Compound 42), Glu-Pro-Val-Pro-Gln-Ala (Compound 43), Pro-Val-Pro-Gln-Ala-Lys (Compound 44), Glu-Pro-Val-Pro-Gln-Ala-Arg (Compound 45),

[0022] Ala-Pro-Val-Pro-Gln-Ala-Lys (Compound 46), Glu-Pro-Val-Pro-Ala-Ala-Lys (Compound 47), Glu-Pro-Val-Pro-Gln-Ala-Ala (Compound 48), Asp-Pro-Val-Pro-Gln-Ala-Lys (Compound 49), Asn-Pro-Val-Pro-Gln-Ala-Lys (Compound 50), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala (Compound 51), Glu-Pro-Ala-Pro-Gln-Ala-Lys (Compound 52), Glu-Ala-Val-Pro-Gln-Ala-Lys (Compound 53), Glu-Pro-Val-Ala-Gln-Ala-Lys (Compound 54), Glu-Pro-Val-Pro-Glu-Ala-Lys (Compound 55), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val (Compound 56), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (Compound 57), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro (Compound 58), Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (Compound 59), Pro-Val-Pro-Gln-Ala-Lys-Pro (Compound 60),

[0023] D-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 61), Lys-D-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 62), Lys-Glu-D-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 63), Lys-Glu-Pro-D-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 64), Lys-Glu-Pro-Val-D-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 65), Lys-Glu-Pro-Val-Pro-D-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 66), Lys-Glu-Pro-Val-Pro-Gln-D-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 67), Lys-Glu-Pro-Val-Pro-Gln-Ala-D-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 68), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-D-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 69), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-D-Arg-Lys-Val-Ala-Ala-Gln (compound 70), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-D-Lys-Val-Ala-Ala-Gln (compound 71), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-D-Val-Ala-Ala-Gln (compound 72), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-D-Ala-Ala-Gln (compound 73), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-D-Ala-Gln (compound 74), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-D-Gln (Compound 75),

[0024] Glu-Gly-Val-Pro-Gln-Ala-Lys (Compound 76), Glu-Pro-Val-Gly-Gln-Ala-Lys (Compound 77), D-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 78), Glu-D-Pro-Val-Pro-Gln-Ala-Lys (Compound 79), Glu-Pro-D-Val-Pro-Gln-Ala-Lys (Compound 80), Glu-Pro-Val-D-Pro-Gln-Ala-Lys (Compound 81), Glu-Pro-Val-Pro-D-Gln-Ala-Lys (Compound 82), Glu-Pro-Val-Pro-Gln-D-Ala-Lys (Compound 83), Glu-Pro-Val-Pro-Gln-Ala-D-Lys (Compound 84), Lys-Glu-Pro-Val-Pro (Compound 85), Glu-Pro-Val-Pro-Gln (Compound 86), Lys-Glu-Pro-Val-Pro-Gln (Compound 87), Val-Pro-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 88), Pyro-Glu-Leu-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 89), Pro-Ala-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 90),

[0025] Arg-Lys-Asp-Val-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 91), Arg-Lys-Asp-Val-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 92), Arg-Lys-Asp-Val-Tyr-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 93), Arg-Lys-Asp-Val-Tyr-Pro-Val-Pro-Gln (Compound 94), Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 95), Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Glu-Pro-Val-Pro-Gln-Ala-Lys(compound96)、 Ser-Ser-Glu-Asp-Ile-Lys-Glu-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 97), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 98), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Pro-Val-Pro-Gln(compound99)、 Val-Pro-Pro-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln(compound100)、 Glu-Pro-Val-Pro-Gln-Ala-Lys-Ser-Ser-Glu-Asp-Ile-Lys-Glu (Compound 101), Glu-Pro-Val-Pro-Gln-Ala-Lys-Val-Pro-Tyr(compound102)、 Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Glu (compound 103), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Asn (compound 104), Lys-Gln-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln(compound105)、 Lys-Glu-Pro-Ile-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 106), Val-Pro-Gln-Ala (Compound 107), or It is selected from Val-Pro-Gln-Ala-Lys (compound 108).

[0026] In one embodiment, the compound is Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 1), Lys-Glu-D-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 63), Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 96), Val-Pro-Pro-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 100), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Asn (compound 104), Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 6), Pro-Val-Pro-Gln (compound 12), Glu-Pro-Val-Ala-Gln-Ala-Lys (compound 54), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (compound 57), Lys-Glu-Pro-Val-Pro-Gln-Ala-D-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 68), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-D-Val-Ala-Ala-Gln (compound 72), Pyro-Glu-Leu-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 89),

[0027] Arg-Lys-Asp-Val-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 92), Arg-Lys-Asp-Val-Tyr-Pro-Val-Pro-Gln (Compound 94), Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 95), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 97), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 98), Lys-Gln-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 105), Lys-Glu-Pro-Ile-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 106), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 4), Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 5), Glu-Pro-Val-Pro (Compound 9), Lys-Pro-Arg-Lys (Compound 10), Arg-Lys-Val-Ala (Compound 15), Lys-Glu-Pro-Ala-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 25),

[0028] Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Ala-Arg-Lys-Val-Ala-Ala-Gln (compound 26), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Ala-Ala-Ala-Gln (compound 29), Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 31), Lys-Glu-Pro-Val-Gly-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (compound 34), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys (Compound 38), Glu-Pro-Val-Pro-Gln-Ala-Ala (Compound 48), Asp-Pro-Val-Pro-Gln-Ala-Lys (Compound 49), Asn-Pro-Val-Pro-Gln-Ala-Lys (Compound 50), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala (Compound 51), Glu-Ala-Val-Pro-Gln-Ala-Lys (Compound 53), Glu-Pro-Val-Pro-Glu-Ala-Lys (Compound 55), Lys-D-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 62), Lys-Glu-Pro-Val-D-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 65), Lys-Glu-Pro-Val-Pro-D-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 66), Lys-Glu-Pro-Val-Pro-Gln-D-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 67), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-D-Arg-Lys-Val-Ala-Ala-Gln (compound 70),

[0029] Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-D-Gln (compound 75), Glu-Pro-Val-Pro-Gln-D-Ala-Lys (compound 83), Lys-Glu-Pro-Val-Pro (compound 85), Glu-Pro-Val-Pro-Gln (compound 86), Val-Pro-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 88), Pro-Ala-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 90), Arg-Lys-Asp-Val-Tyr-Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 93), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Pro-Val-Pro-Gln (compound 99), or It is selected from Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Glu (compound 103).

[0030] According to a second aspect, the present invention provides the use of the polypeptide compound or a physiologically acceptable salt thereof in the manufacture of a medicament for treating enteritis, or a method for treating enteritis comprising administering a therapeutically effective amount of the polypeptide compound or a physiologically acceptable salt thereof to a subject, or the polypeptide compound or a physiologically acceptable salt thereof for treating enteritis. Further, enteritis includes specific enteritis and non-specific enteritis. Further, specific enteritis includes inflammatory bowel disease, necrotizing enteropathy, and intestinal dysbiosis. Additionally, inflammatory bowel disease includes ulcerative colitis.

[0031] The present invention further provides a pharmaceutical composition comprising a polypeptide compound or a physiologically acceptable salt of the present invention and a medicamentable excipient. Additionally, drug dosage forms include tablets, capsules, solutions, powders, and pills. The beneficial effects of the novel polypeptide provided by the present invention and its applications are as follows:

[0032] The peptide chain of the polypeptide described in the present invention is short, so that it is absorbed faster and better.The experimental results show that the polypeptide provided by the present application has a clear alleviating effect on the expansion of the intestinal cavity in the rat acute inflammatory bowel disease model test, and has a significant therapeutic effect in the rat acute inflammatory bowel disease model test.The polypeptide described in the present invention has a significant alleviating effect on colitis, and can be used to manufacture drugs for treating colitis, especially for ulcerative colitis. [Brief description of the drawings]

[0033] [Figure 1] 1 shows a schematic diagram of the steps of solid-phase synthesis of a polypeptide. [Diagram 2] The mass spectrum of the polypeptide is shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] The following is provided to illustrate the present invention in conjunction with specific tests, but is not intended to limit the scope of the invention.

[0035] As used in this application (including the appended claims), singular words such as "a," "an," and "the" include their corresponding plural referents unless the context dictates otherwise.

[0036] Unless the context clearly indicates otherwise, the term "or" means, and is used interchangeably with, the term "and / or."

[0037] The term "effective amount" or "therapeutically effective amount" refers to an amount of an active ingredient (e.g., a compound) that, when administered to a subject for treating a disease or at least one clinical symptom of a disease or disorder, is sufficient to affect the treatment of said disease, disorder, or condition. A "therapeutically effective amount" varies with the compound, the disease, disorder, and / or symptoms of the disease or disorder, the severity of the disease, disorder, and / or symptoms of the disease or disorder, the age of the subject being treated, and / or the weight of the subject being treated. The appropriate amount in any given situation will be apparent to one of skill in the art or can be determined by routine experimentation. In some embodiments, a "therapeutically effective amount" is an effective amount of at least one compound disclosed herein and / or at least one stereoisomer thereof, and / or at least one medicament salt thereof, in the "treatment" (as defined above) of a disease or disorder of a subject. In the case of combination therapy, a "therapeutically effective amount" refers to the total amount of the combined subjects that effectively treats a disease, disorder, or condition.

[0038] The term "physiologically compatible salts" refers to salt forms that are physiologically compatible (i.e., pharmacologically acceptable) and essentially non-toxic to the individual to whom the compound of the present invention is administered. Physiologically compatible salts of the compounds of the present invention include conventional stoichiometric acid addition salts or base addition salts formed from appropriate non-toxic organic or inorganic acids or inorganic bases.

[0039] The term "intestinal dilatation" refers to intestinal dilatation or intestinal dilatation. In patients with enteritis, the intestine with intestinal dilatation caused by various factors such as intestinal damage, mucus exudation, accumulation of gas or liquid in the intestine, and overgrowth of microorganisms is thicker than the normal intestine, and recurrent enteritis such as intestinal dilatation due to inflammatory bowel disease or intestinal dilatation or intestinal obstruction due to tumors is often seen clinically.

[0040] As used herein, the abbreviations for each amino acid sequence are as follows: JPEG2025502306000001.jpg117121

[0041] JPEG2025502306000002.jpg89163

[0042] Example 1: Chemical synthesis of polypeptides The polypeptide compound was synthesized by a conventional solid-phase synthesis method using a fully automated polypeptide synthesizer, and chemical synthesis of the polypeptide was performed through resin swelling, deprotection, washing, amino acid activation, and condensation processes. A schematic diagram of the polypeptide solid-phase synthesis steps is shown in Figure 1, using Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 1) as an example.

[0043] Step 1, Preparation of fully protected peptide resin (1) Swelling of resin: 7.71 g (SD=0.73 mmol / g) of 2-chlorotriyl chloride resin was weighed out, added to a synthesis tube equipped with a sieve plate, and swelled with 100 ml of dichloromethane (DCM). (2) Preparation of Fmoc-Gln(Trt)-resin: Fmoc-Gln(Trt)-OH and DIPEA were weighed out and added to a synthesis tube in a molar ratio of 1:1.78:4.31. Nitrogen gas (N 2 The resin was bubbled and shaken with dimethylformamide (DMF) for 1 to 3 hours, sucked dry, washed five times with 100 ml each time, and sucked dry. (3) Removal of Fmoc protecting group: 100 ml of 20% piperidine-DMF (v / v) solution was added to a reactor, and the reaction was carried out by bubbling nitrogen gas for 20 minutes. The reaction was then dried by suction, and the reaction mixture was washed five times with DMF, 100 ml per wash, for 3 minutes per wash, and then dried by suction. The removal of Fmoc was detected by the ninhydrin method.

[0044] (4) Preactivation of amino acid: 15 mmol of Fmoc-protected amino acid, 15 mmol of HOBt, and 15 mmol of DIC were added to a 250 ml beaker, dissolved in 100 ml of DMF, and stirred at room temperature for preparation for use. (5) Amino acid coupling: The already activated protected amino acid solution was poured into the reactor, and the reactor was washed by refilling with an appropriate amount of DCM. The reaction was carried out by bubbling nitrogen gas at room temperature for 1 to 3 hours, and the ninhydrin method was used to detect whether the amino acid coupling was complete. If it was complete, the resin was dried by suction. The resin was washed five times with DMF at 100 ml / time, 3 min / time, and then dried by suction. The dosage of each amino acid and condensation agent is shown in Table 2. (6) After the first amino acid condensation was completed, steps (4) and (5) were repeated to extend the peptide chain in the order of amino acids until the final amino acid coupling was completed. (7) The resin peptide was washed four times with DMF at 150 ml / time for 3 min / time, and then washed five times with DCM at 150 ml / time for 3 min / time, and then dried by suction.

[0045] JPEG2025502306000003.jpg100170

[0046] Step 2, Disconnect (1) Add a cleavage agent (TFA:TIPS:H) to the synthesis tube. 2 Then, nitrogen gas was bubbled through the mixture for 1.5 to 3 hours to carry out the reaction. (2) After the cleavage reaction was completed, the cleavage agent was suction filtered into a 250 ml round-bottom flask. After vacuum concentration to one-fourth of the original cleavage agent volume, 10 times the existing volume of methyl tert-butyl ether was added and allowed to settle to obtain a white solid. The resulting mixture was filtered and washed three times with 50 ml of methyl tert-butyl ether each, and the resulting crude peptide was placed in a sand funnel and dried using nitrogen gas in a fume hood, and the solvent was volatilized until the crude peptide was in powder form. 9.04 g of crude peptide was obtained, with a crude yield of 74.7%.

[0047] Step 3: Purification, salt exchange and lyophilization Direct salt exchange (acetate) by polypeptide HPLC A. Chromatographic Parameters Chromatography column: Dynamic axial compression column 80 x 250 mm, packing: Daisogel C18 (SP-100-8-ODS-P) Eluent A1: 0.1M acetic acid Eluent A2: 0.025M acetic acid - 0.1M ammonium acetate Eluent B: Acetonitrile Flow rate: 180ml / min UV detection wavelength: 220nm

[0048] B. Operation steps a) Dissolve crude peptide in water and / or acetonitrile, then filter through a 0.45 μm filter membrane. b) Equilibration of a chromatographic column with 95% A1 + 5% B c) injection d) Equilibration of a chromatographic column with 95% A2 + 5% B e) Gradient elution of A1 and B f) Collection of the target peptide eluate g) Rotary evaporation and concentration h) Freeze drying 8.26 g of the crude peptide was purified to give 4.92 g of pure peptide, giving a purification yield of 59.5%. Other compounds were synthesized in a manner similar to that of compound 1. The results are shown in Table 3 and elsewhere in the specification.

[0049] JPEG2025502306000004.jpg238170

[0050] JPEG2025502306000005.jpg246170

[0051] JPEG2025502306000006.jpg240170

[0052] JPEG2025502306000007.jpg251170

[0053] JPEG2025502306000008.jpg250170

[0054] NOTE: A doubly charged peak represents the target molecule bound to two protons, a triple charged peak represents the target molecule bound to three protons, and N / A represents that the actual weight is not included due to the difficulty in weighing.

[0055] Compound 1: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High resolution mass spectrometry (TOF-HRMS), molecular formula: C 73 H 127 N 23 O 20 ;m / z:m / z:549.65904([M+3H] 3+ ), 823.98493([M+2H] 2+ ), 1646.96346([M+H] + ). 1 H NMR (600MHz, D 2 O+CD 3 CN)δ4.48(dd,J=9.5,4.1Hz,1H)4.42(dd,J=9.2,4.5Hz,1H)4.32-4.27(m,1H)4.27-4.21(m,3H )4.20-4.07(m,6H)4.00(dd,J=8.3,4.8Hz,1H)3.95(d,J=7.5Hz,1H)3.86(t,J=6.7Hz,1H)3.77 -3.62(m,3H)3.59-3.43(m,3H)3.04(t,J=6.7Hz,2H)2.87-2.78(m,6H)2.28-2.08(m,9H)2.00- 1.80(m,31H,AcOH)1.80-1.41(m,23H)1.40-1.24(m,6H)1.24-1.18(m,9H)0.87-0.73(m,12H).

[0056] Compound 2: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys (acetate) High-resolution mass spectrometry (TOF-HRMS), molecular formula: C 57 H 100 N 18 O 15 ; m / z: 426.59680 ([M + 3H] 3+ )、639.39021 ([M + 2H] 2+ )、1277.77023 ([M + H] + ). 1H NMR (600 MHz, DMSO-d6) δ 4.57 (dd, J = 8.7, 4.9 Hz, 1H) 4.41 - 4.11 (m, 10H) 3.83 (s, 1H) 3.78 (t, J = 6.5 Hz, 1H) 3.54 (d, J = 73.5 Hz, 7H) 3.08 (d, J = 7.0 Hz, 2H) 2.74 - 2.68 (m, 7H) 2.32 (d, J = 9.1 Hz, 2H) 2.23 - 2.17 (m, 2H) 2.05 - 1.46 (m, AcOH, 56H) 1.43 - 1.22 (m, 7H) 1.17 (d, J = 7.0 Hz, 3H) 0.82 (dd, J = 19.6, 6.7 Hz, 6H).

[0057] Compound 3: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (acetate) High-resolution mass spectrometry (TOF-HRMS), molecular formula: C 51 H 88 N 16 O 14 ; m / z: 383.89927 ([M + 3H] 3+ )、575.34276 ([M + 2H] 2+ )、1149.67551 ([M + H] + ). 1 H NMR (600 MHz, DMSO-d 6) δ 4.58 - 4.55 (m, 1H) 4.44 - 4.37 (m, 2H) 4.33 (dd, J = 8.4, 4.2 Hz, 1H) 4.30 - 4.22 (m, 3H) 4.16 - 4.12 (m, 2H) 3.79 (d, J = 6.1 Hz, 1H) 3.64 - 3.48 (m, 6H) 3.08 (t, J = 7.0 Hz, 2H) 2.71 (d, J = 8.2 Hz, 5H) 2.36 - 2.30 (m, 2H) 2.15 (t, J = 7.6 Hz, 2H) 2.09 - 1.41 (m, AcOH, 46H) 1.37 - 1.29 (m, 4H) 1.16 (d, J = 7.1 Hz, 3H) 0.85 (dd, J = 20.7, 6.7 Hz, 6H).

[0058] Compound 4: Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 40 H 69 N 11 O 12 ; m / z: 448.76653 ([M + 2H] 2+ )、896.52058 ([M + H] + ). 1 H NMR (600 MHz, DMSO - d 6 ) δ 4.56 (dd, J = 9.0, 4.9 Hz, 1H) 4.39 (dd, J = 8.3, 4.4 Hz, 1H) 4.31 - 4.24 (m, 3H) 4.13 (dd, J = 9.1, 5.1 Hz, 2H) 3.78 (dd, J = 7.9, 4.3 Hz, 1H) 3.67 - 3.51 (m, 4H) 2.75 - 2.70 (m, 4H) 2.38 - 2.29 (m, 2H) 2.14 (t, J = 7.8 Hz, 2H) 2.04 - 1.47 (m, AcOH, 33H) 1.35 - 1.28 (m, 4H) 1.19 (d, J = 7.2 Hz, 3H) 0.85 (dd, J = 22.1, 6.8 Hz, 6H).

[0059] Compound 5: Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 33 H 60 N 12 O 9; m / z: 385.24021 ([M + 2H] 2+ ), 769.46971 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.23 - 4.17 (m, 1H) 4.15 - 4.07 (m, 4H) 3.95 (dd, J = 8.5, 4.8 Hz, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.25 - 3.15 (m, 2H) 3.00 (t, J = 7.0 Hz, 2H) 2.78 (t, J = 7.7 Hz, 2H) 2.30 - 2.22 (m, 1H) 2.12 - 2.05 (m, 2H) 1.93 - 1.80 (m, 5H) 1.75 (s, AcOH, 10H) 1.62 - 1.40 (m, 8H) 1.19 (d, J = 7.2 Hz, 8H) 0.73 (dd, J = 6.7, 4.0 Hz, 6H).

[0060] Compound 6: Glu - Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 34 H 57 N 9 O 11 ; m / z: 768.42641 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.46 (dd, J = 8.4, 6.4 Hz, 1H) 4.35 - 4.27 (m, 3H) 4.26 - 4.18 (m, 2H) 4.09 (dd, J = 8.2, 5.1 Hz, 1H) 3.84 - 3.77 (m, 1H) 3.68 - 3.52 (m, 3H) 2.91 (t, J = 7.5 Hz, 2H) 2.39 (t, J = 7.2 Hz, 2H) 2.33 (t, J = 7.6 Hz, 2H) 2.27 - 2.17 (m, 2H) 2.12 - 1.87 (m, AcOH, 13H) 1.83 - 1.72 (m, 3H) 1.66 - 1.57 (m, 3H) 1.32 (dd, J = 11.8, 7.5 Hz, 5H) 0.92 (dd, J = 12.6, 6.7 Hz, 6H).

[0061] Compound 7: Lys - Glu - Pro - Val (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C21 H 37 N 5 O 7 ; m / z: 472.27768 ([M+H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.43 (dd, J = 10.2, 4.0 Hz, 1H) 4.27 (dd, J = 8.3, 5.3 Hz, 1H) 3.85 - 3.80 (m, 2H) 3.68 - 3.60 (m, 1H) 3.59 - 3.46 (m, 1H) 2.80 (t, J = 7.6 Hz, 2H) 2.22 - 2.14 (m, 2H) 2.10 - 2.06 (m, 1H) 1.96 - 1.64 (m, AcOH, 11H) 1.52 - 1.47 (m, 2H) 1.29 - 1.22 (m, 2H) 0.71 (dd, J = 15.3, 6.9 Hz, 6H).

[0062] Compound 8: Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 16 H 29 N 5 O 6 ; m / z: 388.2187 ([M+H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.25 (q, J = 7.2 Hz, 1H) 4.17 (q, J = 7.2 Hz, 1H) 4.05 (dd, J = 8.5, 4.8 Hz, 1H) 3.67 (d, J = 6.0 Hz, 1H) 2.23 - 2.14 (m, 2H) 2.13 - 2.05 (m, 1H) 2.04 - 1.95 (m, 1H) 1.85 - 1.76 (m, 1H) 1.28 (dd, J = 7.2, 5.0 Hz, 6H) 0.90 (dd, J = 10.3, 6.9 Hz, 6H).

[0063] Compound 9: Glu - Pro - Val - Pro (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 20 H 32 N 4 O 7 ; 441.23562 ([M+H] + ). 1 1H NMR (600 MHz, DMSO-d 6 ) δ 4.42 (dd, J = 8.4, 4.6 Hz, 1H) 4.28 (t, J = 8.3 Hz, 1H) 4.17 (dd, J = 8.5, 4.7 Hz, 1H) 3.78 (dd, J = 8.3, 4.2 Hz, 1H) 3.64 - 3.45 (m, 4H) 2.37 - 2.27 (m, 2H) 2.08 - 1.58 (m, AcOH, 16H) 0.87 (dd, J = 25.7, 6.7 Hz, 6H).

[0064] Compound 10: Lys - Pro - Arg - Lys (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 23 H 45 N 9 O 5 ; 264.68527 ([M + 2H] 2+ )、528.36210 ([M + H] + ). 1 1H NMR (600 MHz, DMSO-d 6 ) δ 4.42 (dd, J = 8.2, 5.2 Hz, 1H) 4.23 (t, J = 6.7 Hz, 1H) 4.14 (dd, J = 8.9, 5.2 Hz, 1H) 4.09 (d, J = 7.9 Hz, 1H) 3.64 (dd, J = 9.9, 6.6 Hz, 1H) 3.45 - 3.40 (m, 1H) 3.07 (s, 2H) 2.72 (t, J = 6.3 Hz, 4H) 2.11 - 2.04 (m, 1H) 1.92 - 1.66 (m, AcOH, 18H) 1.56 - 1.48 (m, 8H) 1.45 - 1.38 (m, 2H) 1.33 - 1.29 (m, 2H).

[0065] Compound 11: Ala - Lys - Pro - Arg (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 20 H 38 N 8 O 5 ; 236.15638 ([M + 2H] 2+ )、471.30462 ([M + H] + ). 1 1H NMR (600 MHz, D 2O)) δ 4.55 (dd, J = 8.3, 5.6 Hz, 1H) 4.34 (dd, J = 8.4, 5.9 Hz, 1H) 4.09 - 3.96 (m, 2H) 3.82 - 3.74 (m, 1H) 3.64 - 3.55 (m, 1H) 3.12 (t, J = 6.9 Hz, 2H) 2.93 (t, J = 7.6 Hz, 2H) 2.28 - 2.20 (m, 1H) 2.04 - 1.83 (m, 3H) 1.82 (s, AcOH, 6H) 1.79 - 1.60 (m, 6H) 1.58 - 1.51 (m, 2H) 1.42 (d, J = 7.1 Hz, 5H).

[0066] Compound 12: Pro - Val - Pro - Gln (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 20 H 33 N 5 O 6 ; m / z: 440.25122 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.33 - 4.18 (m, 3H) 3.97 (dd, J = 8.9, 4.8 Hz, 1H) 3.74 - 3.65 (m, 1H) 3.53 - 3.46 (m, 1H) 3.25 - 3.16 (m, 2H) 2.29 - 2.22 (m, 1H) 2.17 - 2.10 (m, 3H) 1.99 - 1.66 (m, AcOH, 12H) 0.82 (d, J = 6.8 Hz, 3H) 0.76 (d, J = 6.7 Hz, 3H).

[0067] Compound 13: Val - Pro - Gln - Ala (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 18 H 31 N 5 O 6 ; m / z: 414.23575 ([M + H] + ). 1 H NMR (600 MHz, D 2O) δ 4.37 (t, J = 7.5 Hz, 1H) 4.15 (dd, J = 8.6, 6.0 Hz, 1H) 4.07 (d, J = 5.5 Hz, 1H) 4.03 (t, J = 7.2 Hz, 1H) 3.68 - 3.61 (m, 1H) 3.55 - 3.48 (m, 1H) 2.35 - 2.26 (m, 2H) 2.26 - 2.15 (m, 2H) 2.04 - 1.74 (m, AcOH, 7H) 1.22 (d, J = 7.2 Hz, 3H) 0.98 (d, J = 7.0 Hz, 3H) 0.87 (d, J = 6.8 Hz, 3H).

[0068] Compound 14: Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 19 H 34 N 6 O 6 ; m / z: 222.13480 ([M + 2H] 2+ )、443.26183 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.28 (dd, J = 8.7, 6.1 Hz, 1H) 4.25 - 4.15 (m, 2H) 4.01 (dd, J = 8.1, 5.2 Hz, 1H) 3.34 - 3.22 (m, 2H) 2.86 (t, J = 7.5 Hz, 2H) 2.37 - 2.29 (m, 1H) 2.26 (t, J = 7.6 Hz, 2H) 2.00 - 1.84 (m, 5H) 1.73 - 1.64 (m, 1H) 1.62 - 1.50 (m, 3H) 1.30 - 1.24 (m, 5H).

[0069] Compound 15: Arg - Lys - Val - Ala (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 20 H 40 N 8 O 5 ; m / z: 237.16465 ([M + 2H] 2+ )、473.32087 ([M + H] + ). 1 H NMR (600 MHz, D 2O) δ 4.28 (t, J = 7.3 Hz, 1H) 4.00 - 3.94 (m, 2H) 3.90 (t, J = 6.4 Hz, 1H) 3.07 (t, J = 7.0 Hz, 2H) 2.85 (t, J = 7.6 Hz, 2H) 2.01 - 1.92 (m, 1H) 1.80 - 1.75 (m, AcOH, 8H) 1.73 - 1.59 (m, 2H) 1.59 - 1.40 (m, 4H) 1.35 - 1.22 (m, 2H) 1.19 (d, J = 7.2 Hz, 3H) 0.81 (t, J = 6.9 Hz, 6H).

[0070] Compound 16: Lys-Val-Ala-Ala (acetate) High-resolution mass spectrometry (TOF-HRMS), molecular formula: C 17 H 33 N 5 O 5 ; m / z: 388.25660 ([M+H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.18 (q, J = 7.1 Hz, 1H) 4.03 - 3.91 (m, 3H) 2.87 (t, J = 7.7 Hz, 2H) 1.98 - 1.89 (m, 1H) 1.83 - 1.74 (m, AcOH, 6H) 1.60 - 1.53 (m, 2H) 1.36 - 1.27 (m, 2H) 1.26 (d, J = 7.2 Hz, 3H) 1.19 (d, J = 7.2 Hz, 3H) 0.83 (d, J = 6.8 Hz, 6H).

[0071] Compound 17: Gln-Ala-Lys-Pro (acetate) High-resolution mass spectrometry (TOF-HRMS), molecular formula: C 19 H 34 N 6 O 6 ; m / z: 443.26161 ([M+H] + ). 1 H NMR (600 MHz, D 2O) δ 4.48 (dd, J = 8.2, 5.6 Hz, 1H) 4.26 - 4.20 (m, 1H) 4.10 (dd, J = 8.5, 5.4 Hz, 1H) 3.91 (t, J = 6.6 Hz, 1H) 3.68 - 3.61 (m, 1H) 3.55 - 3.43 (m, 1H) 2.88 (t, J = 7.5 Hz, 2H) 2.39 - 2.27 (m, 2H) 2.15 - 1.96 (m, 3H) 1.92 - 1.69 (m, 8H) 1.66 - 1.49 (m, 3H) 1.43 - 1.29 (m, 2H) 1.28 - 1.22 (m, 3H).

[0072] Compound 18: Pro - Arg - Lys - Val (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 22 H 42 N 8 O 5 ; m / z: 250.17158 ([M + 2H] 2+ )、499.33464 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.27 (dd, J = 8.7, 6.0 Hz, 1H) 4.24 - 4.17 (m, 2H) 3.88 (d, J = 6.2 Hz, 1H) 3.33 - 3.20 (m, 2H) 3.09 - 3.02 (m, 2H) 2.85 (t, J = 7.5 Hz, 2H) 2.37 - 2.28 (m, 1H) 1.98 - 1.86 (m, 4H) 1.78 (s, AcOH, 6H) 1.72 - 1.42 (m, 8H) 1.38 - 1.23 (m, 2H) 0.75 (dd, J = 11.2, 6.8 Hz, 6H).

[0073] Compound 19: Ala - Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 70 H 120 N 22 O 20 ; m / z: 530.64499 ([M + 3H] 3+ )、795.46224 ([M + 2H] 2+ )、1589.91350 ([M + H] +). 1 H NMR(600MHz,D 2 O)δ4.53 - 4.43(m,2H)4.33(dd,J = 8.3,6.0Hz,1H)4.27(t,J = 7.7Hz,3H)4.24 - 4.12(m,6H)4.06 - 3.94(m,3H)3.77(q,J = 7.6Hz,1H)3.73 - 3.67(m,2H)3.63 - 3.53(m,2H)3.51(q,J = 7.6Hz,1H)3.08(t,J = 6.9Hz,2H)2.91 - 2.83(m,4H)2.29(t,J = 7.6Hz,2H)2.26 - 2.12(m,7H)2.03 - 1.46(m,AcOH,38H)1.39(d,J = 7.1Hz,4H)1.36 - 1.30(m,2H)1.30 - 1.22(m,10H)0.92 - 0.77(m,12H).

[0074] Compound 20: Lys - Ala - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 71 H 125 N 23 O 18 ; m / z: 530.32804([M + 3H] 3+ )、794.98683([M + 2H] 2+ )、1588.96546([M + H] + ). 1 H NMR(600MHz,D 2O) δ 4.51 (q, J = 7.1 Hz, 1H) 4.48 - 4.43 (m, 1H) 4.31 - 4.25 (m, 3H) 4.24 - 4.11 (m, 6H) 4.03 (dd, J = 8.4, 4.9 Hz, 1H) 3.98 (d, J = 7.6 Hz, 1H) 3.87 (t, J = 6.7 Hz, 1H) 3.79 - 3.67 (m, 3H) 3.60 - 3.47 (m, 3H) 3.08 (t, J = 6.9 Hz, 2H) 2.91 - 2.83 (m, 6H) 2.28 (t, J = 7.6 Hz, 2H) 2.21 - 2.13 (m, 5H) 2.03 - 1.64 (m, AcOH, 33H) 1.64 - 1.47 (m, 11H) 1.44 - 1.28 (m, 6H) 1.28 - 1.21 (m, 12H) 0.89 - 0.76 (m, 12H).

[0075] Compound 21: Lys - Glu - Ala - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (TOF - HRMS), molecular formula: C 71 H 125 N 23 O 20 ; m / z: 540.99125 ([M + 3H] 3+ )、810.98235 ([M + 2H] 2+ )、1620.94722 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.45 (dd, J = 9.4, 4.9 Hz, 1H) 4.30 - 4.24 (m, 3H) 4.24 - 4.11 (m, 8H) 4.02 (dd, J = 8.4, 4.9 Hz, 1H) 3.97 (d, J = 7.6 Hz, 1H) 3.89 (t, J = 6.7 Hz, 1H) 3.79 - 3.66 (m, 2H) 3.60 - 3.47 (m, 2H) 3.08 (t, J = 6.9 Hz, 2H) 2.91 - 2.83 (m, 6H) 2.28 (t, J = 7.6 Hz, 2H) 2.22 - 2.12 (m, 6H) 2.02 - 1.46 (m, AcOH, 41H) 1.43 - 1.28 (m, 6H) 1.28 - 1.20 (m, 12H) 0.88 - 0.75 (m, 12H).

[0076] Compound 22: Lys-Glu-Pro-Val-Ala-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (TOF-HRMS), molecular formula: C 71 H 125 N 23 O 20 ; m / z: 540.99088 ([M + 3H] 3+ )、810.98168 ([M + 2H] 2+ )、1620.95237 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.51 (dd, J = 9.6, 4.4 Hz, 1H) 4.46 (dd, J = 9.4, 4.8 Hz, 1H) 4.35 (dd, J = 8.4, 5.8 Hz, 1H) 4.28 (dd, J = 8.3, 6.1 Hz, 1H) 4.25 - 4.13 (m, 7H) 4.03 (dd, J = 8.3, 4.9 Hz, 1H) 3.98 (d, J = 7.6 Hz, 1H) 3.94 - 3.88 (m, 2H) 3.75 - 3.67 (m, 2H) 3.63 - 3.56 (m, 1H) 3.51 (q, J = 7.3 Hz, 1H) 3.09 (t, J = 6.9 Hz, 2H) 2.91 - 2.83 (m, 6H) 2.29 - 2.21 (m, 4H) 2.21 - 2.13 (m, 4H) 2.03 - 1.65 (m, AcOH, 31H) 1.64 - 1.46 (m, 11H) 1.45 - 1.28 (m, 6H) 1.28 - 1.22 (m, 12H) 0.89 - 0.78 (m, 12H).

[0077] Compound 23: Lys-Glu-Pro-Val-Pro-Ala-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 71 H 124 N 22 O 19 ; m / z: 398.24191 ([M + 4H] 4+ )、530.65344 ([M + 3H] 3+ )、795.97791 ([M + 2H] 2+ ). 1 H NMR (600MHz, D 2 O)δ4.51(dd,J=9.6,4.4Hz,1H)4.44(dd,J=9.4,4.9Hz,1H)4.33(dd,J=8.4,5.8Hz,1H)4.31-4.08(m,9H) 4.03(dd,J=8.4,4.9Hz,1H)3.97(d,J=7.6Hz,1H)3.92-3.87(m,1H)3.79-3.73(m,1H)3.73-3.66(m,2H)3. 62-3.52(m,2H)3.51-3.46(m,1H)3.07(t,J=6.9Hz,2H)2.90-2.81(m,6H)2.29-2.21(m,2H)2.21-2.10(m, 5H)2.02-1.64(m,AcOH,37H)1.64-1.45(m,11H)1.44-1.27(m,6H)1.27-1.20(m,12H)0.91-0.74(m,12H).

[0078] Compound 24: Lys-Glu-Pro-Val-Pro-Gln-Ala-Ala-Pro-Arg-Lys-Val-Ala-Ala-Gln (hydrogen acid) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 70 H 120 N 22 O 20 ;m / z:398.23245([M+4H] 4+ )、530.64075([M+3H] 3+ )、795.45752([M+2H] 2+ ). 1 H NMR (600MHz, D 2O) δ 4.51 (dd, J = 9.7, 4.4 Hz, 1H) 4.45 (q, J = 7.1 Hz, 1H) 4.33 (dd, J = 8.4, 5.8 Hz, 1H) 4.31 - 4.24 (m, 3H) 4.23 - 4.12 (m, 6H) 4.03 (dd, J = 8.4, 4.8 Hz, 1H) 3.97 (d, J = 7.6 Hz, 1H) 3.92 - 3.87 (m, 1H) 3.79 - 3.73 (m, 1H) 3.73 - 3.64 (m, 2H) 3.62 - 3.48 (m, 3H) 3.08 (t, J = 6.9 Hz, 2H) 2.91 - 2.83 (m, 4H) 2.32 - 2.21 (m, 4H) 2.20 - 2.11 (m, 5H) 2.03 - 1.71 (m, AcOH, 32H) 1.71 - 1.45 (m, 10H) 1.37 - 1.27 (m, 4H) 1.27 - 1.17 (m, 12H) 0.90 - 0.76 (m, 12H).

[0079] Compound 25: Lys - Glu - Pro - Ala - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 71 H 123 N 23 O 20 ; m / z: 405.48935 ([M + 4H] 4+ )、540.31677 ([M + 3H] 3+ )、809.97144 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2O) δ 4.51 (dd, J = 9.5, 4.4 Hz, 1H) 4.48 - 4.41 (m, 2H) 4.32 - 4.25 (m, 3H) 4.21 (dd, J = 8.1, 6.7 Hz, 1H) 4.19 - 4.12 (m, 5H) 4.02 (dd, J = 8.4, 4.9 Hz, 1H) 3.97 (d, J = 7.6 Hz, 1H) 3.92 - 3.85 (m, 1H) 3.74 - 3.64 (m, 3H) 3.60 - 3.46 (m, 3H) 3.07 (t, J = 6.9 Hz, 2H) 2.90 - 2.83 (m, 6H) 2.30 - 2.20 (m, 4H) 2.20 - 2.12 (m, 5H) 2.02 - 1.45 (m, AcOH, 48H) 1.43 - 1.27 (m, 6H) 1.27 - 1.21 (m, 12H) 0.80 (dd, J = 6.8, 4.4 Hz, 6H).

[0080] Compound 26: Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys - Ala - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 71 H 125 N 23 O 20 ; m / z: 405.99350 ([M + 4H] 4+ )、540.98883 ([M + 3H] 3+ )、810.97961 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.51 (dd, J = 9.6, 4.4 Hz, 1H) 4.33 (dd, J = 8.4, 5.8 Hz, 1H) 4.31 - 4.23 (m, 2H) 4.23 - 4.09 (m, 8H) 4.03 (dd, J = 8.4, 4.9 Hz, 1H) 3.97 (d, J = 7.6 Hz, 1H) 3.93 - 3.86 (m, 1H) 3.81 - 3.66 (m, 2H) 3.62 - 3.52 (m, 2H) 3.07 (t, J = 6.9 Hz, 2H) 2.86 (m, 6H) 2.31 - 2.11 (m, 8H) 2.03 - 1.41 (m, AcOH, 48H) 1.40 - 1.27 (m, 6H) 1.25 (dd, J = 13.7, 7.3 Hz, 12H) 0.90 - 0.76 (m, 12H).

[0081] Compound 27: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Ala-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 70 H 120 N 20 O 20 ; m / z: 391.23177 ([M+4H] 4+ )、781.45496 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.52 - 4.43 (m, 2H) 4.33 (dd, J = 8.4, 5.8 Hz, 1H) 4.31 - 4.22 (m, 3H) 4.21 - 4.10 (m, 6H) 4.02 (dd, J = 8.5, 4.8 Hz, 1H) 3.96 (d, J = 7.7 Hz, 1H) 3.92 - 3.84 (m, 1H) 3.81 - 3.73 (m, 1H) 3.73 - 3.65 (m, 2H) 3.61 - 3.52 (m, 2H) 3.52 - 3.45 (m, 1H) 2.91 - 2.81 (m, 6H) 2.30 - 2.10 (m, 9H) 2.02 - 1.62 (m, AcOH, 31H) 1.62 - 1.51 (m, 8H) 1.41 - 1.27 (m, 6H) 1.27 - 1.20 (m, 12H) 0.90 - 0.75 (m, 12H).

[0082] Compound 28: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Ala-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 70 H 120 N 22 O 20 ; m / z: 398.23303 ([M+4H] 4+ )、530.64142 ([M+3H] 3+ )、795.45850 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2O) δ 4.52 - 4.42 (m, 2H) 4.33 (dd, J = 8.4, 5.8 Hz, 1H) 4.30 - 4.24 (m, 3H) 4.23 - 4.09 (m, 6H) 4.02 (dd, J = 8.5, 4.8 Hz, 1H) 3.95 (d, J = 7.5 Hz, 1H) 3.92 - 3.85 (m, 1H) 3.79 - 3.73 (m, 1H) 3.72 - 3.67 (m, 2H) 3.62 - 3.42 (m, 3H) 3.08 (t, J = 6.9 Hz, 2H) 2.87 (t, J = 7.6 Hz, 4H) 2.30 - 2.25 (m, 2H) 2.24 - 2.10 (m, 7H) 2.02 - 1.65 (m, AcOH, 29H) 1.64 - 1.48 (m, 8H) 1.42 - 1.29 (m, 4H) 1.28 - 1.19 (m, 12H) 0.90 - 0.75 (m, 12H).

[0083] Compound 29: Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Ala - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 71 H 123 N 23 O 20 ; m / z: 405.48969 ([M + 4H] 4+ )、540.31714 ([M + 3H] 3+ )、809.97205 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.49 (dd, J = 9.6, 4.3 Hz, 1H) 4.45 (dd, J = 9.3, 4.9 Hz, 1H) 4.33 (dd, J = 8.4, 5.8 Hz, 1H) 4.29 - 4.24 (m, 3H) 4.19 - 4.13 (m, 7H) 4.02 (dd, J = 8.4, 4.8 Hz, 1H) 3.89 (t, J = 6.8 Hz, 1H) 3.79 - 3.66 (m, 3H) 3.61 - 3.47 (m, 3H) 3.08 (t, J = 6.9 Hz, 2H) 2.86 (q, J = 8.0 Hz, 6H) 2.28 (t, J = 7.6 Hz, 2H) 2.23 - 2.13 (m, 7H) 2.02 - 1.46 (m, AcOH, 47H) 1.42 - 1.18 (m, 20H) 0.85 (dd, J = 14.2, 6.7 Hz, 6H).

[0084] Compound 30: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Ala (acetate) High-resolution mass spectrometry (TOF-HRMS), molecular formula: C 71 H 124 N 22 O 19 ; m / z: 398.24493 ([M + 4H] 4+ )、530.65551 ([M + 3H] 3+ )、795.47815 ([M + 2H] 2+ )、1589.94194 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.51 (dd, J = 9.6, 4.4 Hz, 1H) 4.46 (dd, J = 9.4, 4.9 Hz, 1H) 4.34 (dd, J = 8.4, 5.8 Hz, 1H) 4.31 - 4.24 (m, 3H) 4.24 - 4.20 (m, 1H) 4.20 - 4.09 (m, 5H) 4.02 - 3.96 (m, 2H) 3.93 - 3.86 (m, 1H) 3.80 - 3.74 (m, 1H) 3.74 - 3.67 (m, 2H) 3.63 - 3.43 (m, 3H) 3.08 (t, J = 6.9 Hz, 2H) 2.91 - 2.82 (m, 6H) 2.31 - 2.12 (m, 7H) 2.01 - 1.65 (m, AcOH, 34H) 1.64 - 1.46 (m, 11H) 1.35 (dd, J = 16.0, 8.1 Hz, 6H) 1.27 - 1.20 (m, 12H) 0.92 - 0.77 (m, 12H).

[0085] Compound 31: Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (TOF-HRMS), molecular formula: C 70 H 123 N 23 O 20 ; m / z: 402.49240 ([M + 4H] 4+ )、536.31955 ([M + 3H] 3+ )、803.97442 ([M + 2H] 2+)、1606.91471([M+H] + ). 1 H NMR (600 MHz, D 2 O)δ4.45(dd,J=9.4,4.9Hz,1H)4.32(d,J=8.1Hz,1H)4.30-4.25(m,2H)4.24-4.19(m,2H)4.19-4.11(m,5H)4 .02(dd,J=8.4,4.9Hz,1H)3.97(d,J=7.6Hz,1H)3.91-3.84(m,2H)3.82-3.73(m,2H)3.69(q,J=7.7,7.0Hz,1H )3.59-3.52(m,1H)3.52-3.46(m,1H)3.07(t,J=6.9Hz,2H)2.90-2.82(m,6H)2.28(t,J=7.6Hz,2H)2.23-2.1 2(m,6H)2.02-1.64(m,AcOH,35H)1.63-1.45(m,11H)1.44-1.27(m,6H)1.27-1.21(m,9H)0.88-0.73(m,12H).

[0086] Compound 32: Lys-Glu-Pro-Val-Gly-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (hydrogen acid) High resolution mass spectrometry (TOF-HRMS), molecular formula: C 70 H 123 N 23 O 20 ;m / z:402.49278([M+4H] 4+ )、536.31975([M+3H] 3+ )、803.97422([M+2H] 2+ )、1606.92969([M+H] + ). 1 H NMR (600 MHz, D 2O)δ4.51(dd,J=9.7,4.4Hz,1H)4.46(dd,J=9.4,4.9Hz,1H)4.36(dd,J=8.3,5.9Hz,1H)4.28(dd,J=8.3,6.1Hz,1 H)4.24-4.14(m,6H)4.03(dd,J=8.3,4.9Hz,1H)3.97(dd,J=10.0,7.5Hz,2H)3.90(t,J=6.8Hz,1H)3.87-3.78(m, 2H)3.76-3.67(m,2H)3.61-3.54(m,1H)3.54-3.47(m,1H)3.08(t,J=6.9Hz,2H)2.91-2.83(m,6H)2.26-2.13(m,8 H)2.03-1.87(m,9H)1.87-1.45(m,AcOH,33H)1.44-1.28(m,6H)1.26(dd,J=18.4,7.2Hz,9H)0.89-0.79(m,12H).

[0087] Compound 33: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (hydrogen acid) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 70 H 123 N 23 O 20 ;m / z:402.48917([M+4H] 4+ )、536.31647([M+3H] 3+ )、803.97101([M+2H] 2+ ). 1 H NMR (600MHz, D 2O) δ 4.51 (dd, J = 9.6, 4.4 Hz, 1H) 4.34 (dd, J = 8.4, 5.8 Hz, 1H) 4.31 - 4.11 (m, 9H) 4.03 (dd, J = 8.4, 4.9 Hz, 1H) 3.97 (d, J = 7.6 Hz, 1H) 3.92 - 3.86 (m, 1H) 3.85 - 3.74 (m, 3H) 3.74 - 3.66 (m, 1H) 3.62 - 3.52 (m, 2H) 3.06 (t, J = 7.0 Hz, 2H) 2.91 - 2.83 (m, 6H) 2.31 - 2.11 (m, 8H) 2.03 - 1.43 (m, AcOH, 45H) 1.40 - 1.27 (m, 6H) 1.27 - 1.23 (m, 9H) 0.91 - 0.77 (m, 12H).

[0088] Compound 34: Lys - Glu - Pro - Val - Gly - Gln - Ala - Lys - Gly - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 67 H 119 N 23 O 20 ; m / z: 392.48178 ([M + 4H] 4+ )、522.97314 ([M + 3H] 3+ )、784.45752 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.51 (dd, J = 9.6, 4.4 Hz, 1H) 4.35 (dd, J = 8.3, 5.9 Hz, 1H) 4.25 - 4.12 (m, 7H) 4.03 (dd, J = 8.4, 4.8 Hz, 1H) 3.96 (dd, J = 10.6, 7.5 Hz, 2H) 3.92 - 3.86 (m, 1H) 3.85 - 3.77 (m, 4H) 3.75 - 3.68 (m, 1H) 3.60 - 3.53 (m, 1H) 3.06 (t, J = 7.0 Hz, 2H) 2.92 - 2.83 (m, 6H) 2.28 - 2.12 (m, 7H) 2.05 - 1.41 (m, AcOH, 42H) 1.40 - 1.27 (m, 6H) 1.27 - 1.24 (m, 9H) 0.85 (dd, J = 11.0, 6.7 Hz, 6H) 0.80 (dd, J = 6.8, 5.1 Hz, 6H).

[0089] Compound 35: Lys-Glu-Gly-Val-Gly-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 64 H 115 N 23 O 20 ; m / z: 382.47363 ([M+4H] 4+ )、509.62903 ([M+3H] 3+ )、763.93982 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.27 - 4.13 (m, 8H) 4.05 - 4.00 (m, 2H) 3.97 (d, J = 7.6 Hz, 1H) 3.93 - 3.87 (m, 2H) 3.85 - 3.76 (m, 5H) 3.06 (t, J = 7.0 Hz, 2H) 2.90 - 2.83 (m, 6H) 2.24 - 2.12 (m, 6H) 2.02 - 1.41 (m, AcOH, 40H) 1.39 - 1.27 (m, 6H) 1.27 - 1.22 (m, 9H) 0.85 - 0.76 (m, 12H).

[0090] Compound 36: Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-Gly-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 67 H 119 N 23 O 20 ; m / z: 392.48172 ([M+4H] 4+ )、522.97314 ([M+3H] 3+ )、783.95605 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2O) δ 4.32 (d, J = 8.0 Hz, 1H) 4.28 (dd, J = 8.2, 6.7 Hz, 1H) 4.25 - 4.12 (m, 8H) 4.03 (dd, J = 8.4, 4.8 Hz, 1H) 3.97 (d, J = 7.6 Hz, 1H) 3.92 - 3.83 (m, 2H) 3.83 - 3.73 (m, 4H) 3.60 - 3.53 (m, 1H) 3.06 (t, J = 7.0 Hz, 2H) 2.91 - 2.83 (m, 6H) 2.28 (t, J = 7.5 Hz, 2H) 2.24 - 2.12 (m, 5H) 2.02 - 1.42 (m, AcOH, 43H) 1.41 - 1.27 (m, 6H) 1.27 - 1.22 (m, 9H) 0.91 - 0.72 (m, 12H).

[0091] Compound 37: Lys - Glu - Gly - Val - Gly - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 67 H 119 N 23 O 20 ; m / z: 392.48172 ([M + 4H] 4+ )、522.97314 ([M + 3H] 3+ )、783.95605 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.44 (dd, J = 9.4, 4.9 Hz, 1H) 4.29 - 4.12 (m, 8H) 4.04 - 3.99 (m, 2H) 3.96 (d, J = 7.6 Hz, 1H) 3.91 - 3.82 (m, 3H) 3.81 (s, 2H) 3.72 - 3.65 (m, 1H) 3.52 - 3.44 (m, 1H) 3.06 (t, J = 6.9 Hz, 2H) 2.89 - 2.81 (m, 6H) 2.23 - 2.12 (m, 7H) 2.01 - 1.45 (m, AcOH, 43H) 1.42 - 1.26 (m, 6H) 1.26 - 1.20 (m, 9H) 0.83 - 0.77 (m, 12H).

[0092] Compound 38: Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 51 H 88 N 16 O 14 ; m / z: 383.89569 ([M+3H] 3+ )、575.33978 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ4.45 (dd, J=9.2, 5.0 Hz, 1H) 4.39 (dd, J=8.3, 6.4 Hz, 1H) 4.29-4.21 (m, 4H) 4.19-4.12 (m, 3H) 4.01 (dd, J=7.8, 5.5 Hz, 1H) 3.78-3.73 (m, 1H) 3.72-3.67 (m, 1H) 3.61-3.48 (m, 4H) 3.08 (t, J=6.8 Hz, 2H) 2.88-2.83 (m, 4H) 2.30-2.26 (m, 4H) 2.20-2.13 (m, 3H) 2.08-1.46 (m, AcOH, 38H) 1.39-1.22 (m, 7H) 0.86 (dd, J=10.3, 6.7 Hz, 6H).

[0093] Compound 39: Pro-Val-Pro-Gln-Ala (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 23 H 38 N 6 O 7 ; m / z: 511.2871 ([M+H] + ). 1 H NMR (600 MHz, D 2 O) δ4.41 (d, J=7.3 Hz, 1H) 4.38-4.32 (m, 2H) 4.20 (dd, J=8.7, 5.9 Hz, 1H) 4.11-4.04 (m, 1H) 3.85-3.77 (m, 1H) 3.62 (dt, J=10.3, 7.2 Hz, 1H) 3.39-3.29 (m, 2H) 2.39-2.31 (m, 3H) 2.28-2.20 (m, 1H) 2.08-1.90 (m, AcOH, 10H) 1.86-1.80 (m, 1H) 1.26 (d, J=7.3 Hz, 3H) 0.94 (d, J=6.8 Hz, 3H) 0.88 (d, J=6.8 Hz, 3H).

[0094] Compound 40: Pro-Val-Pro-Glu-Ala (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 23 H 37 N 5 O 8 ; m / z: 512.27081 ([M+H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.41 (d, J = 7.3 Hz, 1H) 4.38 - 4.32 (m, 2H) 4.23 (dd, J = 8.9, 5.6 Hz, 1H) 4.13 - 4.09 (m, 1H) 3.86 - 3.76 (m, 1H) 3.62 (dt, J = 10.2, 7.2 Hz, 1H) 3.38 - 3.28 (m, 2H) 2.43 - 2.35 (m, 3H) 2.26 - 2.16 (m, 1H) 2.12 - 1.72 (m, AcOH, 12H) 1.28 (d, J = 7.2 Hz, 3H) 0.94 (d, J = 6.8 Hz, 3H) 0.87 (d, J = 6.8 Hz, 3H).

[0095] Compound 41: Pro-Val-Pro-Ile-Ala (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 24 H 41 N 5 O 6 ; m / z: 496.31158 ([M+H] + ). 1 H NMR (600 MHz, D 2O) δ 4.36 - 4.27 (m, 3H), 4.03 (q, J = 7.2 Hz, 1H), 3.98 (d, J = 7.8 Hz, 1H), 3.79 - 3.72 (m, 1H), 3.60 - 3.53 (m, 1H), 3.34 - 3.21 (m, 2H), 2.36 - 2.25 (m, 1H), 2.21 - 2.12 (m, 1H), 2.03 - 1.96 (m, 1H), 1.96 - 1.81 (m, AcOH, 7H), 1.80 - 1.69 (m, 2H), 1.43 - 1.33 (m, 1H), 1.20 (d, J = 7.2 Hz, 3H), 1.13 - 1.02 (m, 1H), 0.88 (d, J = 6.8 Hz, 3H), 0.85 - 0.80 (m, 6H), 0.80 - 0.77 (m, 1H), 0.74 (t, J = 7.4 Hz, 3H).

[0096] Compound 42: Pro - Val - Pro - Ala High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 18 H 30 N 4 O 5 ; m / z: 383.22791 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.36 (d, J = 7.2 Hz, 1H), 4.30 (dd, J = 8.5, 6.3 Hz, 1H), 4.24 (dd, J = 8.1, 6.5 Hz, 1H), 4.00 (q, J = 7.2 Hz, 1H), 3.79 - 3.72 (m, 1H), 3.60 - 3.52 (m, 1H), 3.31 - 3.23 (m, 2H), 2.33 - 2.26 (m, 1H), 2.20 - 2.13 (m, 1H), 2.09 - 1.69 (m, AcOH, 10H), 1.21 (d, J = 7.3 Hz, 3H), 0.88 (d, J = 6.9 Hz, 3H), 0.81 (d, J = 6.8 Hz, 3H).

[0097] Compound 43: Glu - Pro - Val - Pro - Gln - Ala (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 28 H 45 N 7 O 10 ; m / z: 640.32892 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.34 (dd, J = 8.3, 6.5 Hz, 1H) 4.25 - 4.15 (m, 3H) 4.08 (dd, J = 8.8, 5.9 Hz, 1H) 4.04 - 4.00 (m, 1H) 3.73 - 3.65 (m, 1H) 3.57 - 3.41 (m, 3H) 2.35 (t, J = 7.3 Hz, 2H) 2.24 - 2.20 (m, 2H) 2.16 - 2.07 (m, 2H) 2.04 - 1.75 (m, AcOH, 11H) 1.73 - 1.63 (m, 2H) 1.17 (d, J = 7.2 Hz, 3H) 0.80 (dd, J = 12.9, 6.8 Hz, 6H).

[0098] Compound 44: Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 29 H 50 N 8 O 8 ; m / z: 320.19421 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.29 - 4.19 (m, 3H) 4.13 - 4.06 (m, 2H) 3.95 (dd, J = 8.2, 5.1 Hz, 1H) 3.73 - 3.68 (m, 1H) 3.52 - 3.47 (m, 1H) 3.24 - 3.16 (m, 2H) 2.79 (t, J = 7.5 Hz, 2H) 2.25 - 2.19 (m, 3H) 2.14 - 2.08 (m, 1H) 1.97 - 1.57 (m, AcOH, 17H) 1.53 - 1.45 (m, 3H) 1.21 - 1.17 (m, 5H) 0.82 (d, J = 6.8 Hz, 3H) 0.75 (d, J = 6.7 Hz, 3H).

[0099] Compound 45: Glu - Pro - Val - Pro - Gln - Ala - Arg (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 34 H 57 N 11 O 11 ; m / z: 398.71835 ([M + 2H] 2+ ), 796.42944 ([M + H]+ ). 1 H NMR(600MHz,D 2 O)δ4.38(dd,J=8.3,6.4Hz,1H)4.27 - 4.19(m,3H)4.19 - 4.10(m,2H)4.03(dd,J=8.3,4.9Hz,1H)3.78 - 3.70(m,1H)3.60 - 3.46(m,3H)3.07 - 3.02(m,2H)2.30(t,J=7.2Hz,2H)2.25(t,J=7.6Hz,2H)2.19 - 2.11(m,2H)2.06 - 1.78(m,AcOH,12H)1.76 - 1.67(m,3H)1.60 - 1.53(m,1H)1.48 - 1.42(m,2H)1.24(d,J=7.1Hz,3H)0.85(dd,J=12.8,6.7Hz,6H)

[0100] Compound 46: Ala - Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 32 H 55 N 9 O 9 ; m / z: 355.71259([M + 2H] 2+ )、710.41809([M + H] + ). 1 H NMR(600MHz,DMSO - d 6)δ8.23(d,J=7.7Hz,1H)8.08(d,J=8.1Hz,1H)7.87(d,J=8.4Hz,1H)7.68(s,1H)7.38(d,J=6.4Hz,1H)6.75(s,1H)4.40-4.37( m,1H)4.33-4.25(m,3H)4.15(t,J=7.2Hz,3H)3.78(d,J=6.4Hz,1H)3.66(dd,J=32.4,8.0Hz,2H)3.58-3.51(m,2H)3.43(d,J= 7.0Hz,1H)3.36-3.27(m,1H)2.67(t,J=7.7Hz,3H)2.19-2.07(m,4H)2.01-1.69(m,AcOH,24H)1.63-1.60(m,1H)1.55-1.41(m ,5H)1.26(d,1H)1.18(d,J=7.2Hz,6H)1.11(d,J=6.7Hz,3H)1.04(d,J=6.6Hz,1H)0.87(d,J=6.7Hz,3H)0.83(d,J=6.9Hz,3H).

[0101] Compound 47: Glu-Pro-Val-Pro-Ala-Ala-Lys (hydrogen hydroxide) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 32 H 54 N 8 O 10 ;m / z:356.20514([M+2H] 2+ )、711.40198([M+H] + ). 1 H NMR (600MHz, D 2 O)δ4.45(dd,J=8.4,6.4Hz,1H)4.33-4.27(m,3H)4.21(dd,J=15.1,7.2Hz,2H)4.07(dd,J=8.1,5.1Hz,1H)3.86-3.75(m,1H)3.67-3.54(m,3H)2.91 (t,J=7.5Hz,2H)2.37(t,J=6.9Hz,2H)2.26-2.18(m,2H)2.14-1.69(m,Ac OH,13H)1.65-1.58(m,3H)1.35-1.29(m,9H)0.92(dd,J=13.6,6.8Hz,6H).

[0102] Compound 48: Glu-Pro-Val-Pro-Gln-Ala-Ala (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 31 H 50 N 8 O 11 ; m / z: 356.18692 ([M+2H] 2+ )、711.36597 ([M+H] + ). 1 H NMR (600 MHz, D 2 O) δ4.34 (dd, J = 8.3, 6.5 Hz, 1H) 4.24 - 4.16 (m, 3H) 4.12 - 4.06 (m, 2H) 4.03 - 3.99 (m, 1H) 3.73 - 3.65 (m, 1H) 3.56 - 3.41 (m, 3H) 2.35 (t, J = 7.3 Hz, 2H) 2.22 - 2.18 (m, 2H) 2.15 - 2.07 (m, 2H) 2.04 - 1.73 (m, AcOH, 11H) 1.71 - 1.63 (m, 2H) 1.18 (dd, J = 11.2, 7.2 Hz, 6H) 0.80 (dd, J = 13.0, 6.8 Hz, 6H).

[0103] Compound 49: Asp-Pro-Val-Pro-Gln-Ala-Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 33 H 55 N 9 O 11 ; m / z: 377.70767 ([M+2H] 2+ )、754.40814 ([M+H] + ). 1 H NMR (600 MHz, D 2O) δ 4.36 - 4.29 (m, 2H), 4.23 - 4.14 (m, 2H), 4.13 - 4.06 (m, 2H), 3.97 (dd, J = 8.3, 5.0 Hz, 1H), 3.74 - 3.65 (m, 1H), 3.56 - 3.46 (m, 2H), 3.44 - 3.39 (m, 1H), 2.79 (t, J = 7.5 Hz, 2H), 2.65 (dd, J = 17.5, 3.3 Hz, 1H), 2.38 (dd, J = 17.5, 10.7 Hz, 1H), 2.21 (t, J = 7.6 Hz, 2H), 2.15 - 2.06 (m, 2H), 1.93 - 1.75 (m, AcOH, 9H), 1.72 - 1.61 (m, 3H), 1.54 - 1.45 (m, 3H), 1.21 (dd, J = 13.1, 7.5 Hz, 5H), 0.80 (dd, J = 11.0, 6.7 Hz, 6H).

[0104] Compound 50: Asn - Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 33 H 56 N 10 O 10 ; m / z: 377.21542 ([M + 2H] 2+ )、753.42365 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.55 (dd, J = 9.3, 4.0 Hz, 1H), 4.47 (dd, J = 8.4, 6.1 Hz, 1H), 4.34 - 4.29 (m, 2H), 4.26 - 4.19 (m, 2H), 4.07 (dd, J = 8.1, 5.1 Hz, 1H), 3.83 - 3.77 (m, 1H), 3.69 - 3.53 (m, 3H), 2.94 - 2.90 (m, 3H), 2.72 (dd, J = 17.0, 9.3 Hz, 1H), 2.33 (t, J = 7.6 Hz, 2H), 2.27 - 2.19 (m, 2H), 2.05 - 1.71 (m, AcOH, 15H), 1.65 - 1.57 (m, 3H), 1.34 - 1.30 (m, 5H), 0.91 (dd, J = 13.4, 6.7 Hz, 6H).

[0105] Compound 51: Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 59 H 102 N 18 O 16 ; m / z: 440.59735 ([M + 3H] 3+ )、660.39252 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.38 (dd, J = 9.3, 4.8 Hz, 1H) 4.33 (dd, J = 8.3, 6.5 Hz, 1H) 4.22 - 4.12 (m, 5H) 4.10 - 4.04 (m, 3H) 3.93 - 3.88 (m, 2H) 3.75 - 3.67 (m, 1H) 3.66 - 3.58 (m, 1H) 3.56 - 3.41 (m, 4H) 3.00 (t, J = 6.9 Hz, 2H) 2.82 - 2.76 (m, 4H) 2.24 - 2.19 (m, 4H) 2.14 - 2.06 (m, 3H) 1.97 - 1.41 (m, AcOH, 37H) 1.33 - 1.12 (m, 10H) 0.80 (dd, J = 9.7, 6.7 Hz, 6H) 0.74 (dd, J = 11.0, 6.8 Hz, 6H).

[0106] Compound 52: Glu - Pro - Ala - Pro - Gln - Ala - Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 32 H 53 N 9 O 11 ; m / z: 370.6998 ([M + 2H] 2+ )、740.39221 ([M + H] + ). 1 H NMR (600 MHz, D 2O) δ 4.43 (q, J = 7.1 Hz, 1H) 4.33 (dd, J = 8.4, 6.5 Hz, 1H) 4.26 (dd, J = 8.4, 5.8 Hz, 1H) 4.22 (dd, J = 7.6, 4.6 Hz, 1H) 4.18 - 4.11 (m, 2H) 4.01 (dd, J = 8.3, 5.0 Hz, 1H) 3.67 (dt, J = 10.0, 6.7 Hz, 1H) 3.61 - 3.54 (m, 1H) 3.53 - 3.44 (m, 2H) 2.84 (t, J = 7.5 Hz, 2H) 2.30 (t, J = 7.2 Hz, 2H) 2.25 (t, J = 7.6 Hz, 2H) 2.21 - 2.12 (m, 2H) 2.08 - 1.77 (m, AcOH, 11H) 1.77 - 1.63 (m, 3H) 1.60 - 1.49 (m, 3H) 1.24 (dd, J = 10.4, 7.1 Hz, 6H).

[0107] Compound 53: Glu - Ala - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 32 H 55 N 9 O 11 ; m / z: 371.7081 ([M + 2H] 2+ )、742.4089 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.23 - 4.18 (m, 3H) 4.13 - 4.06 (m, 2H) 3.95 (dd, J = 8.3, 5.0 Hz, 1H) 3.85 - 3.82 (m, 1H) 3.73 - 3.66 (m, 1H) 3.53 - 3.47 (m, 1H) 2.79 (t, J = 7.5 Hz, 2H) 2.22 - 2.17 (m, 4H) 2.13 - 2.07 (m, 1H) 1.99 - 1.70 (m, AcOH, 9H) 1.69 - 1.59 (m, 2H) 1.53 - 1.45 (m, 3H) 1.26 - 1.12 (m, 9H) 0.79 (d, J = 6.7 Hz, 3H) 0.76 (d, J = 6.7 Hz, 3H).

[0108] Compound 54: Glu - Pro - Val - Ala - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 32H 55 N 9 O 11 ;m / z:371.70767([M+2H] 2+ )、742.40802([M+H] + ). 1 H NMR (600 MHz, DMSO-d 6 +D 2 O)δ4.34(dd,J=8.3,6.0Hz,1H)4.15-4.05(m,4H)3.97-3.87(m,2H)3.51(d,J=9.8Hz,1H)3.46-3.38(m,1H)2.74(t,J=7.5Hz,2H)2.23( t,J=7.1Hz,2H)2.17-2.06(m,3H)1.95-1.67(m,AcOH,10H)1.65-1.59(m,1H)1.53-1.42(m,3H)1.22-1.13(m,8H)0.78(d,J=6.8Hz,6H).

[0109] Compound 55:Glu-Pro-Val-Pro-Glu-Ala-Lys (Hydroxygenate) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 34 H 56 N 8 O 12 ;m / z:385.2083([M+2H] 2+ )、769.4092([M+H] + ). 1 H NMR (600MHz, D 2 O)δ4.33(dd,J=8.3,6.5Hz,1H)4.21-4.16(m,3H)4.11(t,J=7.1Hz,1H)4.07(dd,J=8 .8,5.7Hz,1H)3.98(dd,J=8.5,4.8Hz,1H)3.71-3.66(m,1H)3.55-3.41(m,3H)2.78(t ,J=7.5Hz,2H)2.36-2.14(m,5H)2.13-2.05(m,2H)1.99-1.74(m,AcOH,11H)1.70-1.6 1(m,3H)1.53-1.45(m,3H)1.20(dd,J=15.4,7.5Hz,5H)0.80(dd,J=12.5,6.7Hz,6H).

[0110] Compound 56: Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 56 H 97 N 17 O 15 ; m / z: 416.91827 ([M+3H] 3+ )、624.87354 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.43 (dd, J = 9.3, 4.9 Hz, 1H) 4.38 (dd, J = 8.4, 6.4 Hz, 1H) 4.27 - 4.19 (m, 5H) 4.16 - 4.10 (m, 3H) 3.88 (d, J = 6.2 Hz, 1H) 3.74 (dt, J = 10.1, 6.9 Hz, 1H) 3.71 - 3.63 (m, 1H) 3.60 - 3.46 (m, 4H) 3.07 - 3.02 (m, 2H) 2.87 - 2.82 (m, 4H) 2.29 - 2.24 (m, 4H) 2.19 - 2.11 (m, 3H) 2.04 - 1.43 (m, AcOH, 37H) 1.37 - 1.20 (m, 7H) 0.85 (dd, J = 10.1, 6.8 Hz, 6H) 0.74 (dd, J = 11.8, 6.9 Hz, 6H).

[0111] Compound 57: Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 45 H 76 N 14 O 13 ; m / z: 511.29254 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2O) δ 4.39 (dd, J = 8.6, 5.5 Hz, 1H) 4.32 (dd, J = 8.3, 6.5 Hz, 1H) 4.22 - 4.13 (m, 4H) 4.10 - 4.03 (m, 2H) 3.93 (dd, J = 7.9, 5.2 Hz, 1H) 3.72 - 3.60 (m, 2H) 3.54 - 3.40 (m, 4H) 3.00 (t, J = 6.9 Hz, 2H) 2.80 (t, J = 7.5 Hz, 2H) 2.24 - 2.18 (m, 4H) 2.14 - 2.06 (m, 3H) 1.98 - 1.70 (m, AcOH, 19H) 1.69 - 1.60 (m, 4H) 1.55 - 1.47 (m, 4H) 1.45 - 1.39 (m, 2H) 1.34 - 1.24 (m, 2H) 1.16 (d, J = 7.1 Hz, 3H) 0.80 (dd, J = 10.4, 6.7 Hz, 6H).

[0112] Compound 58: Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 39 H 64 N 10 O 12 ; m / z: 433.24188 ([M + 2H] 2+ )、865.47662 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.41 (dd, J = 8.5, 5.5 Hz, 1H) 4.33 (dd, J = 8.3, 6.5 Hz, 1H) 4.22 - 4.14 (m, 3H) 4.11 - 4.02 (m, 3H) 3.75 - 3.67 (m, 1H) 3.59 - 3.41 (m, 5H) 2.81 (t, J = 7.4 Hz, 2H) 2.25 - 2.19 (m, 4H) 2.15 - 1.61 (m, AcOH, 26H) 1.57 - 1.48 (m, 3H) 1.37 - 1.23 (m, 2H) 1.16 (d, J = 7.0 Hz, 3H) 0.80 (dd, J = 11.5, 6.7 Hz, 6H).

[0113] Compound 59: Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 40 H69 N 13 O 10 ;m / z:298.18314([M+3H] 3+ )、446.77118([M+2H] 2+ )、892.53497([M+H] + ). 1 H NMR (600 MHz, D 2 O)δ4.40(dd,J=8.6,5.5Hz,1H)4.30-4.19(m,4H)4.11-4.05(m,2H)3.93(dd,J=7.9,5.2H z,1H)3.73-3.63(m,2H)3.52-3.45(m,2H)3.26-3.17(m,2H)3.01(t,J=6.9Hz,2H)2.81(t ,J=7.5Hz,2H)2.26-2.19(m,3H)2.14-2.09(m,2H)1.94-1.62(m,AcOH,24H)1.57-1.40(m ,7H)1.34-1.26(m,2H)1.16(d,J=7.3Hz,3H)0.82(d,J=6.8Hz,3H)0.76(d,J=6.7Hz,3H).

[0114] Compound 60: Pro-Val-Pro-Gln-Ala-Lys-Pro (hydrogen acid) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 34 H 57 N 9 O 9 ;m / z:368.7207([M+2H] 2+ )、736.4343([M+H] + ). 1 H NMR (600 MHz, D 2O) δ 4.46 (dd, J = 8.4, 5.6 Hz, 1H) 4.34 (d, J = 7.4 Hz, 1H) 4.29 (dd, J = 8.5, 6.2 Hz, 1H) 4.27 - 4.24 (m, 1H) 4.16 - 4.07 (m, 3H) 3.78 - 3.70 (m, 1H) 3.66 - 3.60 (m, 1H) 3.58 - 3.45 (m, 2H) 3.30 - 3.22 (m, 2H) 2.86 (t, J = 7.5 Hz, 2H) 2.32 - 2.24 (m, 3H) 2.19 - 2.13 (m, 1H) 2.12 - 2.03 (m, 1H) 2.02 - 1.69 (m, AcOH, 19H) 1.61 - 1.52 (m, 3H) 1.42 - 1.27 (m, 2H) 1.23 - 1.20 (m, 3H) 0.87 (d, J = 6.8 Hz, 3H) 0.81 (d, J = 6.7 Hz, 3H).

[0115] Compound 61: D-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4978 ([M + 4H] 4+ )、549.6611 ([M + 3H] 3+ )、823.9882 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.46 - 4.35 (m, 2H) 4.27 (dd, J = 8.3, 6.1 Hz, 1H) 4.22 - 4.04 (m, 9H) 3.96 (dd, J = 8.4, 4.8 Hz, 1H) 3.90 (d, J = 7.7 Hz, 1H) 3.84 (t, J = 6.6 Hz, 1H) 3.74 - 3.59 (m, 3H) 3.56 - 3.38 (m, 3H) 3.01 (t, J = 6.9 Hz, 2H) 2.83 - 2.76 (m, 6H) 2.23 - 2.06 (m, 9H) 1.96 - 1.39 (m, AcOH, 48H) 1.18 (dd, J = 22.0, 7.2 Hz, 15H) 0.83 - 0.67 (m, 12H).

[0116] Compound 62: Lys-D-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4976 ([M + 4H] 4+ )、549.6608 ([M + 3H] 3+ ). 1 H NMR (600 MHz, D 2 O) δ 4.50 (dd, J = 9.8, 4.4 Hz, 1H) 4.37 (dd, J = 9.4, 4.9 Hz, 1H) 4.25 - 4.03 (m, 10H) 3.95 (dd, J = 8.5, 4.8 Hz, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.83 (t, J = 6.6 Hz, 1H) 3.74 - 3.68 (m, 1H) 3.64 - 3.55 (m, 2H) 3.52 - 3.38 (m, 2H) 3.00 (t, J = 6.9 Hz, 2H) 2.83 - 2.75 (m, 6H) 2.20 (t, J = 7.6 Hz, 2H) 2.12 - 2.06 (m, 6H) 1.92 - 1.41 (m, AcOH, 47H) 1.32 - 1.13 (m, 15H) 0.78 (dd, J = 9.7, 6.7 Hz, 6H) 0.73 (dd, J = 6.8, 4.1 Hz, 6H).

[0117] Compound 63: Lys-Glu-D-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4976 ([M + 4H] 4+ )、549.6609 ([M + 3H] 3+ )、823.9878 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2O) δ 4.45 (dd, J = 9.4, 4.4 Hz, 1H) 4.37 (dd, J = 9.4, 4.9 Hz, 1H) 4.29 - 4.25 (m, 1H) 4.21 - 4.04 (m, 8H) 3.96 - 3.94 (m, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.79 (d, J = 6.9 Hz, 1H) 3.68 - 3.59 (m, 2H) 3.54 - 3.35 (m, 3H) 3.00 (t, J = 6.9 Hz, 2H) 2.82 - 2.74 (m, 6H) 2.23 - 2.19 (m, 2H) 2.15 - 2.02 (m, 6H) 1.95 - 1.41 (m, AcOH, 48H) 1.17 (dd, J = 21.6, 7.2 Hz, 15H) 0.83 - 0.64 (m, 12H).

[0118] Compound 64: Lys - Glu - Pro - D - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4978 ([M + 4H] 4+ )、549.6609 ([M + 3H] 3+ )、823.9878 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.46 (dd, J = 10.2, 3.9 Hz, 1H) 4.41 - 4.31 (m, 2H) 4.27 - 4.18 (m, 3H) 4.15 - 4.02 (m, 7H) 3.95 - 3.92 (m, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.83 (t, J = 6.6 Hz, 1H) 3.67 - 3.50 (m, 5H) 3.47 - 3.25 (m, 2H) 3.00 (t, J = 6.9 Hz, 2H) 2.81 - 2.76 (m, 6H) 2.23 - 2.06 (m, 10H) 1.94 - 1.41 (m, AcOH, 50H) 1.17 (dd, J = 19.9, 7.1 Hz, 17H) 0.76 - 0.68 (m, 12H).

[0119] Compound 65: Lys-Glu-Pro-Val-D-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4979 ([M+4H] 4+ )、549.6612 ([M+3H] 3+ )、823.9883 ([M+2H] 2+ ). 1 H NMR (600MHz, D 2 O) δ4.42 (dd, J=9.9, 4.2Hz, 1H) 4.34 (dd, J=9.2, 5.2Hz, 1H) 4.31-4.23 (m, 2H) 4.22-4.18 (m, 2H) 4.15-4.05 (m, 6H) 3.94 (dd, J=8.4, 4.8Hz, 1H) 3.89 (d, J=7.7Hz, 1H) 3.82 (t, J=6.7Hz, 1H) 3.65 (d, J=6.8Hz, 3H) 3.57-3.36 (m, 3H) 3.00 (t, J=6.9Hz, 2H) 2.82-2.75 (m, 6H) 2.18-2.03 (m, 9H) 1.95-1.40 (m, AcOH, 46H) 1.37-1.08 (m, 16H) 0.80-0.68 (m, 12H).

[0120] Compound 66: Lys-Glu-Pro-Val-Pro-D-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4978 ([M+4H] 4+ )、549.6611 ([M+3H] 3+ )、823.9881 ([M+2H] 2+ ). 1 H NMR (600MHz, D 2O) δ 4.44 - 4.35 (m, 2H) 4.26 - 4.04 (m, 10H) 3.94 (dd, J = 8.5, 4.8 Hz, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.82 (t, J = 6.8 Hz, 1H) 3.76 - 3.68 (m, 1H) 3.64 (d, J = 8.7 Hz, 2H) 3.55 - 3.37 (m, 3H) 3.00 (t, J = 6.9 Hz, 2H) 2.83 - 2.75 (m, 6H) 2.19 - 2.05 (m, 9H) 2.02 - 1.38 (m, AcOH, 47H) 1.34 - 1.15 (m, 15H) 0.78 (dd, J = 11.2, 6.7 Hz, 6H) 0.73 (dd, J = 6.7, 3.9 Hz, 6H).

[0121] Compound 67: Lys - Glu - Pro - Val - Pro - Gln - D - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4961 ([M + 4H] 4+ )、549.6615 ([M + 3H] 3+ )、823.9886 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.47 - 4.38 (m, 2H) 4.26 (dd, J = 8.4, 5.8 Hz, 1H) 4.22 - 4.04 (m, 9H) 3.95 (dd, J = 8.5, 4.8 Hz, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.82 (t, J = 6.8 Hz, 1H) 3.74 - 3.56 (m, 3H) 3.54 - 3.35 (m, 3H) 3.00 (t, J = 6.9 Hz, 2H) 2.86 - 2.74 (m, 6H) 2.23 - 2.05 (m, 9H) 1.94 - 1.38 (m, AcOH, 46H) 1.29 - 1.14 (m, 15H) 0.78 (dd, J = 10.5, 6.7 Hz, 6H) 0.73 (dd, J = 6.8, 3.9 Hz, 6H).

[0122] Compound 68: Lys-Glu-Pro-Val-Pro-Gln-Ala-D-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4977 ([M+4H] 4+ )、549.6615 ([M+3H] 3+ )、823.9879 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.47-4.40 (m, 2H) 4.26 (dd, J = 8.4, 5.9 Hz, 1H) 4.23-4.15 (m, 3H) 4.14-4.01 (m, 6H) 3.95 (dd, J = 8.5, 4.8 Hz, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.82 (t, J = 6.8 Hz, 1H) 3.71-3.44 (m, 5H) 3.01 (t, J = 6.9 Hz, 2H) 2.82-2.73 (m, 6H) 2.23-2.05 (m, 9H) 1.93-1.40 (m, AcOH, 46H) 1.30-1.14 (m, 15H) 0.79 (dd, J = 12.5, 6.7 Hz, 6H) 0.73 (dd, J = 6.8, 4.6 Hz, 6H).

[0123] Compound 69: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-D-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4976 ([M+4H] 4+ )、549.6608 ([M+3H] 3+ ). 1 H NMR (600 MHz, D 2O) δ 4.42 (dt, J = 8.2, 4.3 Hz, 2H) 4.26 (dd, J = 8.4, 5.9 Hz, 1H) 4.23 - 4.14 (m, 3H) 4.14 - 4.05 (m, 6H) 3.94 (dd, J = 8.5, 4.8 Hz, 1H) 3.89 (d, J = 7.7 Hz, 1H) 3.81 (q, J = 7.7, 7.2 Hz, 1H) 3.74 - 3.58 (m, 3H) 3.55 - 3.38 (m, 3H) 2.98 (t, J = 7.0 Hz, 2H) 2.82 - 2.75 (m, 6H) 2.23 - 2.05 (m, 9H) 1.93 - 1.13 (m, AcOH, 62H) 0.79 (dd, J = 13.2, 6.7 Hz, 6H) 0.73 (dd, J = 6.8, 4.7 Hz, 6H).

[0124] Compound 70: Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - D - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4978 ([M + 4H] 4+ )、549.6611 ([M + 3H] 3+ )、823.9883 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.45 - 4.36 (m, 2H) 4.27 - 4.14 (m, 6H) 4.12 - 4.05 (m, 4H) 3.95 (dd, J = 8.4, 4.8 Hz, 1H) 3.90 (d, J = 7.7 Hz, 1H) 3.82 (t, J = 6.8 Hz, 1H) 3.66 (dd, J = 35.9, 8.3 Hz, 3H) 3.55 - 3.39 (m, 3H) 2.99 (t, J = 7.0 Hz, 2H) 2.82 - 2.75 (m, 6H) 2.23 - 2.07 (m, 9H) 1.93 - 1.15 (m, AcOH, 63H) 0.79 (dd, J = 13.9, 6.7 Hz, 6H) 0.74 (dd, J = 6.8, 2.0 Hz, 6H).

[0125] Compound 71: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-D-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4976 ([M+4H] 4+ )、549.6609 ([M+3H] 3+ )、823.9878 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.45 - 4.36 (m, 2H) 4.26 (dd, J = 8.4, 5.8 Hz, 1H) 4.22 - 4.16 (m, 3H) 4.12 - 4.05 (m, 6H) 3.96 - 3.91 (m, 2H) 3.82 (t, J = 6.8 Hz, 1H) 3.73 - 3.58 (m, 3H) 3.54 - 3.36 (m, 3H) 3.00 (t, J = 7.0 Hz, 2H) 2.82 - 2.75 (m, 6H) 2.22 - 2.06 (m, 9H) 1.93 - 1.41 (m, AcOH, 45H) 1.32 - 1.14 (m, 15H) 0.79 (dd, J = 13.8, 6.7 Hz, 6H) 0.74 (d, J = 6.8 Hz, 3H) 0.70 (d, J = 6.8 Hz, 3H).

[0126] Compound 72: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-D-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4976 ([M+4H] 4+ )、549.6609 ([M+3H] 3+ )、823.9876 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2O δ 4.45 - 4.35 (m, 2H) 4.26 (dd, J = 8.4, 5.9 Hz, 1H) 4.21 - 4.05 (m, 9H) 3.94 - 3.88 (m, 2H) 3.82 (t, J = 6.8 Hz, 1H) 3.73 - 3.57 (m, 3H) 3.55 - 3.37 (m, 3H) 2.99 (t, J = 6.8 Hz, 2H) 2.82 - 2.75 (m, 6H) 2.23 - 2.06 (m, 9H) 1.96 - 1.36 (m, AcOH, 50H) 1.32 - 1.14 (m, 15H) 0.78 (dd, J = 13.9, 6.7 Hz, 6H) 0.73 (d, J = 6.7 Hz, 6H).

[0127] Compound 73: Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - D - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4977 ([M + 4H] 4+ )、549.6609 ([M + 3H] 3+ )、823.9879 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.48 (dd, J = 9.7, 4.3 Hz, 1H) 4.43 (dd, J = 9.3, 4.9 Hz, 1H) 4.32 (dd, J = 8.4, 5.8 Hz, 1H) 4.27 - 4.23 (m, 3H) 4.21 - 4.17 (m, 3H) 4.15 - 4.10 (m, 3H) 3.97 (dd, J = 9.2, 4.6 Hz, 1H) 3.89 - 3.85 (m, 2H) 3.76 - 3.66 (m, 3H) 3.59 - 3.45 (m, 3H) 3.05 (t, J = 6.9 Hz, 2H) 2.87 - 2.81 (m, 6H) 2.26 (t, J = 7.7 Hz, 2H) 2.22 - 2.12 (m, 7H) 2.00 - 1.48 (m, AcOH, 47H) 1.37 - 1.20 (m, 16H) 0.86 - 0.77 (m, 12H).

[0128] Compound 74: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-D-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4977 ([M+4H] 4+ )、549.6610 ([M+3H] 3+ )、823.9879 ([M+2H] 2+ ). 1 H NMR (600MHz, D 2 O) δ4.48 (dd, J=9.6, 4.3Hz, 1H) 4.44 (dd, J=9.3, 4.9Hz, 1H) 4.32 (dd, J=8.4, 5.8Hz, 1H) 4.28 - 4.17 (m, 5H) 4.17 - 4.09 (m, 4H) 4.05 (dd, J=9.1, 4.7Hz, 1H) 3.95 (d, J=7.7Hz, 1H) 3.88 (t, J=6.8Hz, 1H) 3.78 - 3.63 (m, 3H) 3.60 - 3.37 (m, 3H) 3.06 (t, J=6.9Hz, 2H) 2.89 - 2.81 (m, 6H) 2.29 - 2.09 (m, 9H) 2.02 - 1.46 (m, AcOH, 45H) 1.39 - 1.19 (m, 15H) 0.84 (dd, J=14.0, 6.7Hz, 6H) 0.78 (dd, J=14.3, 6.8Hz, 6H).

[0129] Compound 75: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-D-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 127 N 23 O 20 ; m / z: 412.4978 ([M+4H] 4+ )、549.6611 ([M+3H] 3+ ) 823.9881 ([M+2H] 2+ ). 1 H NMR (600MHz, D 2O) δ 4.49 - 4.42 (m, 2H), 4.32 (dd, J = 8.4, 5.8 Hz, 1H), 4.27 - 4.10 (m, 9H), 4.04 (dd, J = 8.4, 4.6 Hz, 1H), 3.96 (d, J = 7.4 Hz, 1H), 3.90 - 3.84 (m, 1H), 3.73 (d, J = 7.7 Hz, 1H), 3.71 - 3.64 (m, 2H), 3.60 - 3.32 (m, 3H), 3.06 (t, J = 6.9 Hz, 2H), 2.89 - 2.79 (m, 6H), 2.28 - 2.06 (m, 9H), 1.99 - 1.47 (m, AcOH, 44H), 1.39 - 1.18 (m, 15H), 0.84 (dd, J = 13.9, 6.7 Hz, 6H), 0.78 (dd, J = 6.8, 3.3 Hz, 6H).

[0130] Compound 76: Glu - Gly - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 31 H 53 N 9 O 11 ; m / z: 364.7022 ([M + 2H] 2+ )、728.3929 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.30 (d, J = 7.8 Hz, 1H), 4.26 (dd, J = 8.2, 6.7 Hz, 1H), 4.19 - 4.11 (m, 2H), 4.02 (dd, J = 8.3, 5.0 Hz, 1H), 3.95 (t, J = 6.5 Hz, 1H), 3.91 - 3.82 (m, 2H), 3.78 - 3.72 (m, 1H), 3.58 - 3.51 (m, 1H), 2.84 (t, J = 7.5 Hz, 2H), 2.29 - 2.24 (m, 4H), 2.20 - 2.11 (m, 1H), 2.01 - 1.82 (m, AcOH, 10H), 1.77 - 1.65 (m, 2H), 1.60 - 1.50 (m, 3H), 1.25 (dd, J = 7.5, 4.7 Hz, 5H), 0.84 (d, J = 6.8 Hz, 3H), 0.80 (d, J = 6.7 Hz, 3H).

[0131] Compound 77: Glu - Pro - Val - Gly - Gln - Ala - Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 31 H 53 N 9 O 11 ; m / z: 364.7004 ([M+2H] 2+ )、728.3932 ([M+H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.40 (dd, J = 8.3, 6.5 Hz, 1H) 4.23 (dd, J = 7.7, 4.4 Hz, 1H) 4.20 - 4.15 (m, 2H) 4.01 (dd, J = 8.3, 5.1 Hz, 1H) 3.95 (d, J = 7.4 Hz, 1H) 3.83 - 3.76 (m, 2H) 3.63 - 3.55 (m, 1H) 3.50 - 3.45 (m, 1H) 2.85 (t, J = 7.5 Hz, 2H) 2.32 (t, J = 7.2 Hz, 2H) 2.23 - 2.15 (m, 3H) 2.05 - 1.67 (m, AcOH, 12H) 1.59 - 1.50 (m, 3H) 1.26 (dd, J = 9.7, 7.5 Hz, 5H) 0.84 (dd, J = 14.3, 6.8 Hz, 6H).

[0132] Compound 78: D-Glu-Pro-Val-Pro-Gln-Ala-Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 34 H 57 N 9 O 11 ; m / z: 384.716 ([M+2H] 2+ )、768.4245 ([M+H] + ). 1 H NMR (600 MHz, D 2O) δ 4.36 (dd, J = 8.8, 4.3 Hz, 1H) 4.29 - 4.21 (m, 3H) 4.18 - 4.11 (m, 2H) 4.01 (dd, J = 8.2, 5.1 Hz, 1H) 3.78 - 3.72 (m, 1H) 3.63 - 3.49 (m, 3H) 2.84 (t, J = 7.5 Hz, 2H) 2.28 - 2.23 (m, 4H) 2.19 - 2.12 (m, 2H) 1.98 - 1.66 (m, AcOH, 15H) 1.59 - 1.50 (m, 3H) 1.25 (dd, J = 11.6, 7.4 Hz, 5H) 0.85 (dd, J = 15.5, 6.8 Hz, 6H).

[0133] Compound 79: Glu - D - Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 34 H 57 N 9 O 11 ; m / z: 384.7159 ([M + 2H] 2+ )、768.4244 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.36 (dd, J = 8.8, 3.9 Hz, 1H) 4.33 (d, J = 8.1 Hz, 1H) 4.28 (dd, J = 8.3, 6.6 Hz, 1H) 4.23 (dd, J = 7.1, 5.1 Hz, 1H) 4.19 - 4.13 (m, 2H) 4.02 (dd, J = 8.2, 5.1 Hz, 1H) 3.76 - 3.68 (m, 1H) 3.61 - 3.51 (m, 3H) 2.84 (t, J = 7.5 Hz, 2H) 2.31 - 2.06 (m, 7H) 2.00 - 1.66 (m, AcOH, 16H) 1.58 - 1.50 (m, 3H) 1.27 - 1.23 (m, 5H) 0.81 (dd, J = 22.8, 6.7 Hz, 6H).

[0134] Compound 80: Glu - Pro - D - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 34 H 57 N 9 O 11 ; m / z: 384.7158 ([M + 2H]2+ )、768.4241([M+H] + ). 1 1H NMR(600MHz,D 2 2O)δ4.46(d,J=7.3Hz,1H)4.36(dd,J=8.3,6.6Hz,1H)4.30 - 4.20(m,3H)4.17(dd,J=8.1,6.1Hz,1H)4.03 - 4.00(m,1H)3.72 - 3.66(m,1H)3.63 - 3.57(m,2H)3.53 - 3.49(m,1H)2.85(t,J=7.5Hz,2H)2.36 - 2.21(m,6H)2.18 - 2.13(m,1H)2.05 - 1.78(m,AcOH,17H)1.70 - 1.66(m,1H)1.58 - 1.51(m,3H)1.28 - 1.23(m,6H)0.78(dd,J=15.0,6.7Hz,6H).

[0135] Compound 81: Glu - Pro - Val - D - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 34 19 57 36 9 8 11 ; m / z: 384.7157([M + 2H] 2+ )、768.4240([M + H] + ). 1 1H NMR(600MHz,D 2 2O)δ4.43 - 4.30(m,2H)4.28 - 4.21(m,2H)4.21 - 4.13(m,2H)4.03 - 3.98(m,1H)3.72 - 3.53(m,3H)3.50 - 3.44(m,1H)2.85(t,J=7.5Hz,2H)2.33(t,J=7.2Hz,2H)2.23 - 2.11(m,4H)2.07 - 1.74(m,AcOH,14H)1.73 - 1.64(m,2H)1.58 - 1.50(m,3H)1.29 - 1.23(m,5H)0.81(dd,J=15.1,6.7Hz,6H).

[0136] Compound 82: Glu - Pro - Val - Pro - D - Gln - Ala - Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 31 H 53 N 9 O 11 ; m / z: 384.7158 ([M + 2H] 2+ )、768.4242 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.38 (dd, J = 8.3, 6.4 Hz, 1H) 4.27 - 4.14 (m, 5H) 4.03 (dd, J = 8.4, 5.0 Hz, 1H) 3.80 - 3.75 (m, 1H) 3.62 - 3.45 (m, 3H) 2.85 (t, J = 7.5 Hz, 2H) 2.32 (t, J = 7.3 Hz, 2H) 2.24 - 2.12 (m, 4H) 2.09 - 1.67 (m, AcOH, 15H) 1.60 - 1.50 (m, 3H) 1.28 (d, J = 7.3 Hz, 5H) 0.88 - 0.80 (m, 6H).

[0137] Compound 83: Glu - Pro - Val - Pro - Gln - D - Ala - Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 31 H 53 N 9 O 11 ; m / z: 384.7159 ([M + 2H] 2+ )、768.4243 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.38 (dd, J = 8.3, 6.4 Hz, 1H) 4.28 - 4.20 (m, 3H) 4.19 - 4.12 (m, 2H) 4.05 (dd, J = 8.6, 5.0 Hz, 1H) 3.77 - 3.72 (m, 1H) 3.60 - 3.45 (m, 3H) 2.85 - 2.80 (m, 2H) 2.32 (t, J = 7.2 Hz, 2H) 2.26 (t, J = 8.0 Hz, 2H) 2.20 - 2.12 (m, 2H) 2.08 - 1.77 (m, AcOH, 13H) 1.75 - 1.66 (m, 3H) 1.57 - 1.47 (m, 3H) 1.26 - 1.18 (m, 5H) 0.85 (dd, J = 13.0, 6.7 Hz, 6H).

[0138] Compound 84: Glu - Pro - Val - Pro - Gln - Ala - D - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 31 H 53 N 9 O 11 ; m / z: 384.7160 ([M + 2H] 2+ )、768.4246 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ4.39 (dd, J = 8.3, 6.4 Hz, 1H) 4.30 - 4.20 (m, 3H) 4.19 - 4.11 (m, 2H) 4.05 (dd, J = 8.3, 4.8 Hz, 1H) 3.79 - 3.71 (m, 1H) 3.61 - 3.47 (m, 3H) 2.86 - 2.81 (m, 2H) 2.32 (t, J = 7.2 Hz, 2H) 2.27 (t, J = 7.5 Hz, 2H) 2.21 - 2.12 (m, 2H) 2.05 - 1.78 (m, AcOH, 12H) 1.78 - 1.68 (m, 3H) 1.60 - 1.50 (m, 3H) 1.27 - 1.20 (m, 5H) 0.86 (dd, J = 12.5, 6.7 Hz, 6H).

[0139] Compound 85: Lys - Glu - Pro - Val - Pro (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 26 H 44 N 6 O 8 ; m / z: 454.2655 ([M + 2H] 2+ )、569.3287 ([M + H] + ). 1 H NMR (600 MHz, D 2O) δ 4.50 (dd, J = 9.9, 4.2 Hz, 1H) 4.36 - 4.22 (m, 3H) 4.09 (dd, J = 8.5, 5.8 Hz, 1H) 3.89 (t, J = 6.7 Hz, 1H) 3.70 - 3.65 (m, 2H) 3.60 - 3.53 (m, 2H) 3.51 - 3.26 (m, 1H) 2.87 (d, J = 7.5 Hz, 2H) 2.28 - 2.09 (m, 5H) 2.00 - 1.68 (m, AcOH, 18H) 1.58 - 1.55 (m, 2H) 1.35 - 1.29 (m, 2H) 0.88 (d, J = 6.8 Hz, 3H) 0.82 (d, J = 6.7 Hz, 3H).

[0140] Compound 86: Glu - Pro - Val - Pro - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 25 H 40 N 6 O 9 ; m / z: 569.2919 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.40 (dd, J = 8.3, 6.4 Hz, 1H) 4.31 - 4.23 (m, 3H) 4.09 (dd, J = 9.0, 4.8 Hz, 1H) 3.78 - 3.72 (m, 1H) 3.61 - 3.48 (m, 3H) 2.41 (t, J = 7.3 Hz, 2H) 2.25 - 2.14 (m, 4H) 2.09 - 1.70 (m, AcOH, 13H) 0.86 (dd, J = 15.3, 6.7 Hz, 6H).

[0141] Compound 87: Lys - Glu - Pro - Val - Pro - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 31 H 52 N 8 O 10 ; m / z: 349.1971 ([M + 2H] 2+ )、697.3868 ([M + H] + ). 1 H NMR (600 MHz, D 2O) δ 4.51 (dd, J = 9.8, 4.3 Hz, 1H) 4.34 - 4.25 (m, 3H) 4.03 (dd, J = 8.8, 4.7 Hz, 1H) 3.89 (t, J = 6.7 Hz, 1H) 3.79 - 3.65 (m, 2H) 3.63 - 3.52 (m, 2H) 2.86 (t, J = 7.5 Hz, 2H) 2.28 - 2.13 (m, 6H) 2.00 - 1.73 (m, AcOH, 17H) 1.60 - 1.54 (m, 2H) 1.36 - 1.28 (m, 2H) 0.86 (d, J = 6.8 Hz, 3H) 0.83 (d, J = 6.6 Hz, 3H).

[0142] Compound 88: Val - Pro - Tyr - Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 92 H 152 N 26 O 24 ; m / z: 502.2934 ([M + 4H] 4+ )、669.3699 ([M + 3H] 3+ ). 1 H NMR (600 MHz, D 2 O) δ 6.97 - 6.94 (m, 2H) 6.70 - 6.66 (m, 2H) 4.44 (dd, J = 9.4, 4.8 Hz, 1H) 4.35 - 4.08 (m, 17H) 4.05 - 4.00 (m, 2H) 3.96 (d, J = 7.6 Hz, 1H) 3.76 - 3.67 (m, 3H) 3.64 - 3.53 (m, 3H) 3.48 (dd, J = 10.2, 6.3 Hz, 3H) 3.07 (t, J = 6.9 Hz, 2H) 2.94 (dd, J = 13.6, 6.6 Hz, 1H) 2.88 - 2.79 (m, 7H) 2.76 (dd, J = 13.6, 9.2 Hz, 1H) 2.27 (t, J = 7.6 Hz, 2H) 2.21 (t, J = 7.6 Hz, 2H) 2.18 - 2.08 (m, 8H) 2.01 - 1.45 (m, AcOH, 59H) 1.30 - 1.10 (m, 16H) 0.95 (d, J = 6.9 Hz, 3H) 0.87 - 0.77 (m, 18H).

[0143] Compound 89: pyro-Glu-Leu-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 84 H 145 N 25 O 24 ; m / z: 468.7766 ([M + 4H] 4+ )、624.6998 ([M + 3H] 3+ )、936.5460 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.47 - 4.42 (m, 2H) 4.32 - 4.10 (m, 13H) 4.02 (dd, J = 8.4, 4.8 Hz, 1H) 3.96 (d, J = 7.6 Hz, 1H) 3.82 - 3.60 (m, 3H) 3.58 - 3.45 (m, 3H) 3.07 (t, J = 6.9 Hz, 2H) 2.90 - 2.80 (m, 6H) 2.45 - 2.36 (m, 1H) 2.31 - 2.24 (m, 4H) 2.23 - 2.03 (m, 7H) 1.99 - 1.44 (m, AcOH, 47H) 1.39 - 1.19 (m, 15H) 0.85 (dd, J = 12.5, 6.8 Hz, 6H) 0.81 - 0.77 (m, 9H) 0.75 (d, J = 6.0 Hz, 3H).

[0144] Compound 90: Pro-Ala-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 90 H 148 N 26 O 24 ; m / z: 495.2855 ([M + 4H] 4+ )、660.0449 ([M + 3H] 3+ )、989.5637 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2O) δ 6.99 - 6.92 (m, 2H), 6.71 - 6.64 (m, 2H), 4.47 - 4.42 (m, 1H), 4.36 (t, J = 7.8 Hz, 1H), 4.32 - 4.06 (m, 15H), 4.04 - 3.99 (m, 1H), 3.96 (d, J = 7.6 Hz, 1H), 3.79 - 3.65 (m, 3H), 3.60 - 3.46 (m, 3H), 3.30 - 3.22 (m, 2H), 3.07 (t, J = 6.9 Hz, 2H), 2.89 - 2.79 (m, 8H), 2.33 - 2.06 (m, 11H), 1.99 - 1.45 (m, AcOH, 51H), 1.39 - 1.14 (m, 19H), 0.87 - 0.77 (m, 12H).

[0145] Compound 91: Arg - Lys - Asp - Val - Tyr - Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Gln (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 103 H 174 N 32 O 28 ; m / z: 578.0856 ([M + 4H] 4+ )、770.4463 ([M + 3H] 3+ )、1155.1642 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 6.96 (d, J = 8.5 Hz, 2H), 6.70 - 6.64 (m, 2H), 4.50 - 4.43 (m, 2H), 4.38 (t, J = 8.0 Hz, 1H), 4.30 - 4.11 (m, 13H), 4.02 (dd, J = 8.4, 4.9 Hz, 1H), 3.96 (d, J = 7.6 Hz, 1H), 3.94 - 3.90 (m, 2H), 3.79 - 3.65 (m, 3H), 3.62 - 3.46 (m, 3H), 3.11 - 3.05 (m, 4H), 2.88 - 2.79 (m, 10H), 2.51 (dd, J = 15.9, 5.3 Hz, 1H), 2.42 (dd, J = 16.0, 8.5 Hz, 1H), 2.29 - 2.11 (m, 9H), 1.99 - 1.64 (m, AcOH, 45H), 1.63 - 1.45 (m, 19H), 1.41 - 1.14 (m, 18H), 0.87 - 0.77 (m, 12H), 0.72 (d, J = 6.7 Hz, 6H).

[0146] Compound 92: Arg-Lys-Asp-Val-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 70 H 116 N 20 O 20 ; m / z: 390.2233 ([M+4H] 4+ )、519.9619 ([M+3H] 3+ )、779.4393 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ6.96 (d, J = 8.6 Hz, 2H) 6.67 (d, J = 8.5 Hz, 2H) 4.49 (dd, J = 8.4, 5.3 Hz, 1H) 4.38 (t, J = 8.0 Hz, 1H) 4.31 - 4.23 (m, 5H) 4.19 - 4.10 (m, 3H) 4.01 (dd, J = 8.2, 5.1 Hz, 1H) 3.93 - 3.89 (m, 2H) 3.77 - 3.67 (m, 2H) 3.61 - 3.50 (m, 2H) 3.10 - 3.05 (m, 2H) 2.86 - 2.79 (m, 8H) 2.51 (dd, J = 16.0, 5.3 Hz, 1H) 2.42 (dd, J = 15.9, 8.5 Hz, 1H) 2.28 - 2.20 (m, 4H) 2.18 - 2.10 (m, 2H) 1.97 - 1.65 (m, AcOH, 29H) 1.61 - 1.45 (m, 13H) 1.26 (dd, J = 11.1, 7.4 Hz, 10H) 0.83 (dd, J = 19.0, 6.7 Hz, 6H) 0.72 (d, J = 5.6 Hz, 6H).

[0147] Compound 93: Arg-Lys-Asp-Val-Tyr-Glu-Pro-Val-Pro-Gln-Ala-Lys (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 64 H 104 N 18 O 19 ; m / z: 715.3917 ([M+2H] 2+ ). 1H NMR (600MHz, D 2 O)δ6.96(d,J=8.6Hz,2H)6.66(d,J=8.5Hz,2H)4.48-4.42(m,3H)4.26-4.12(m,6H)4.02(dd,J=8.2,5.0Hz,1H) 3.95-3.89(m,2H)3.77-3.68(m,1H)3.56-3.47(m,2H)3.43-3.36(m,1H)3.10-3.04(m,2H)2.87-2.80(m,6H)2.5 4(dd,J=16.0,5.1Hz,1H)2.45(dd,J=16.0,8.4Hz,1H)2.27(t,J=7.6Hz,2H)2.17-2.08(m,4H)1.98-1.66(m,AcO H,27H)1.65-1.45(m,9H)1.26(dd,J=11.3,7.4Hz,7H)0.84(dd,J=13.0,6.7Hz,6H)0.70(dd,J=6.8,2.8Hz,6H).

[0148] Compound 94: Arg-Lys-Asp-Val-Tyr-Pro-Val-Pro-Gln (hydrogen acid) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 50 H 80 N 14 O 14 ;m / z:367.8727([M+3H] 3+ )、551.3051([M+2H] 2+ )、1101.6030([M+H] + ). 1 H NMR (600MHz, D 2O)δ4.45(dd,J=8.9,4.8Hz,1H)4.36-4.22(m,4H)4.04-3.98(m,1H)3.90(dd,J=7.0,5.8Hz,2H)3.76 (dd,J=10.1,6.4Hz,1H)3.69-3.63(m,1H)3.60-3.43(m,2H)3.09-3.05(m,2H)2.95(dd,J=14.3,5.2 Hz,1H)2.86-2.82(m,2H)2.74-2.67(m,1H)2.52-2.31(m,2H)2.22-2.08(m,4H)1.99-1.46(m,AcOH, 29H)1.32-1.23(m,2H)0.90-0.81(m,6H)0.75(dd,J=10.3,6.8Hz,2H)0.67(dd,J=17.1,6.7Hz,4H).

[0149] Compound 95: Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (hydrogen acid) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 113 H 188 N 34 O 31 ;m / z:504.6906([M+5H] 5+ )、630.6115([M+4H] 4+ )、840.4796([M+3H] 3+ ). 1 H NMR (600MHz, D 2O) δ 7.22 (t, J = 7.4 Hz, 2H) 7.16 (t, J = 7.3 Hz, 1H) 7.12 - 7.07 (m, 2H) 4.47 - 4.41 (m, 3H) 4.35 - 4.03 (m, 19H) 4.02 (dd, J = 8.4, 4.8 Hz, 1H) 3.95 (d, J = 3.6 Hz, 1H) 3.86 (s, 1H) 3.75 (s, 1H) 3.68 (t, J = 8.5 Hz, 2H) 3.58 - 3.42 (m, 5H) 3.06 (t, J = 6.9 Hz, 4H) 2.91 - 2.81 (m, 7H) 2.29 - 2.11 (m, 12H) 2.00 - 1.19 (m, AcOH, 80H) 1.14 (d, J = 7.1 Hz, 3H) 1.06 (d, J = 6.3 Hz, 3H) 0.84 (dd, J = 13.7, 6.7 Hz, 6H) 0.81 - 0.76 (m, 9H) 0.72 (d, J = 5.6 Hz, 3H).

[0150] Compound 96: Gly - Pro - Glu - Thr - Ala - Phe - Leu - Arg - Glu - Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 74 H 118 N 20 O 22 ; m / z: 547.2972 ([M + 3H] 3+ )、820.4424 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2O)δ7.21(dd,J=8.2,6.6Hz,2H)7.16(t,J=7.3Hz,1H)7.12-7.07(m,2H)4.50-4.42(m,2H)4.36-4.22(m,4H)4.21-4.09(m,7H) 4.07-4.00(m,2H)3.93(d,J=16.5Hz,1H)3.84(d,J=16.5Hz,1H)3.78-3.70(m,1H)3.68-3.60(m,1H)3.56-3.42(m,4H)3.10-2. 97(m,3H)2.90-2.82(m,3H)2.29-2.09(m,9H)2.00-1.81(m,AcOH,19H)1.77-1.66(m,5H)1.61-1.37(m,9H)1.26(dd,J=11.9,7 .4Hz,5H)1.14(d,J=7.2Hz,3H)1.05(d,J=6.4Hz,3H)0.84(dd,J=15.5,6.7Hz,6H)0.77(d,J=5.9Hz,3H)0.72(d,J=5.7Hz,3H).

[0151] Compound 97:Ser-Ser-Glu-Asp-Ile-Lys-Glu-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (hydrogen hydroxide) High resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 105 H 179 N 31 O 35 ;m / z:488.0708([M+5H] 5+ )、609.8367([M+4H] 4+ )、812.7799([M+3H] 3+ ). 1 H NMR (600MHz, D 2O) δ 4.48 - 4.41 (m, 3H) 4.34 (t, J = 5.4 Hz, 1H) 4.31 (dd, J = 8.4, 5.8 Hz, 1H) 4.28 - 4.22 (m, 3H) 4.22 - 4.09 (m, 11H) 4.04 - 3.88 (m, 5H) 3.81 - 3.72 (m, 3H) 3.71 - 3.62 (m, 2H) 3.59 - 3.43 (m, 3H) 3.07 (t, J = 6.9 Hz, 2H) 2.90 - 2.80 (m, 8H) 2.58 (dd, J = 16.0, 6.3 Hz, 1H) 2.48 (dd, J = 16.0, 7.9 Hz, 1H) 2.29 - 2.09 (m, 13H) 2.00 - 1.47 (m, AcOH, 51H) 1.40 - 1.20 (m, 18H) 1.12 - 1.05 (m, 1H) 0.89 - 0.70 (m, 18H).

[0152] Compound 98: Ser - Ser - Glu - Asp - Ile - Lys - Glu - Glu - Pro - Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 66 H 109 N 17 O 26 ; m / z: 519.5973 ([M + 3H] 3+ )、778.8925 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.54 - 4.47 (m, 2H) 4.37 - 4.30 (m, 2H) 4.27 - 4.10 (m, 8H) 4.05 - 3.99 (m, 2H) 3.94 - 3.88 (m, 2H) 3.79 - 3.73 (m, 3H) 3.70 - 3.62 (m, 1H) 3.61 - 3.50 (m, 2H) 2.85 (t, J = 7.6 Hz, 4H) 2.63 (dd, J = 16.2, 6.2 Hz, 1H) 2.51 (dd, J = 16.2, 7.9 Hz, 1H) 2.37 - 2.06 (m, 11H) 1.99 - 1.49 (m, AcOH, 30H) 1.34 - 1.24 (m, 8H) 1.10 - 1.01 (m, 1H) 0.84 (dd, J = 13.8, 6.7 Hz, 6H) 0.77 - 0.71 (m, 6H).

[0153] Compound 99: Ser-Ser-Glu-Asp-Ile-Lys-Glu-Pro-Val-Pro-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 52 H 85 N 13 O 21 ; m / z: 614.806 ([M + 2H] 2+ )、1228.605 ([M + H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.54 - 4.48 (m, 2H) 4.36 (t, J = 5.5 Hz, 1H) 4.34 - 4.24 (m, 3H) 4.23 - 4.18 (m, 2H) 4.12 - 4.05 (m, 2H) 4.01 (d, J = 7.9 Hz, 1H) 3.94 - 3.88 (m, 2H) 3.79 - 3.72 (m, 3H) 3.70 - 3.62 (m, 1H) 3.60 - 3.50 (m, 2H) 2.85 (t, J = 7.6 Hz, 2H) 2.65 (dd, J = 16.3, 6.0 Hz, 1H) 2.53 (dd, J = 16.4, 8.0 Hz, 1H) 2.40 - 2.03 (m, 9H) 2.01 - 1.51 (m, AcOH, 21H) 1.34 - 1.22 (m, 3H) 1.08 - 1.01 (m, 1H) 0.89 - 0.80 (m, 6H) 0.76 - 0.70 (m, 6H).

[0154] Compound 100: Val-Pro-Pro-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 88 H 150 N 26 O 23 ; m / z: 389.0348 ([M + 5H] 5+ )、480.0415 ([M + 4H] 4+ )、647.7197 ([M + 3H] 3+ ). 1 H NMR (600 MHz, D 2O) δ 4.49 - 4.42 (m, 2H) 4.34 - 4.06 (m, 13H) 4.05 - 4.00 (m, 2H) 3.96 (d, J = 7.6 Hz, 1H) 3.80 - 3.73 (m, 1H) 3.69 (d, J = 9.8 Hz, 4H) 3.58 - 3.45 (m, 5H) 3.07 (t, J = 6.9 Hz, 2H) 2.88 - 2.83 (m, 6H) 2.27 (t, J = 7.7 Hz, 3H) 2.20 - 2.11 (m, 9H) 2.01 - 1.45 (m, AcOH, 55H) 1.24 (dd, J = 21.5, 7.2 Hz, 16H) 0.97 (d, J = 6.9 Hz, 3H) 0.88 - 0.78 (m, 15H).

[0155] Compound 101: Glu - Pro - Val - Pro - Gln - Ala - Lys - Ser - Ser - Glu - Asp - Ile - Lys - Glu (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 66 H 109 N 17 O 26 ; m / z: 519.5978 ([M + 3H] 3+ )、778.8933 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.50 (dd, J = 8.0, 6.0 Hz, 1H) 4.40 (dd, J = 8.4, 6.4 Hz, 1H) 4.36 - 4.30 (m, 2H) 4.27 - 4.19 (m, 6H) 4.18 - 4.11 (m, 2H) 4.08 (dd, J = 8.8, 4.9 Hz, 1H) 4.01 (d, J = 8.1 Hz, 1H) 3.82 - 3.71 (m, 5H) 3.62 - 3.47 (m, 3H) 2.86 (t, J = 7.5 Hz, 4H) 2.65 (dd, J = 16.4, 6.0 Hz, 1H) 2.51 (dd, J = 16.3, 8.1 Hz, 1H) 2.34 (t, J = 7.2 Hz, 2H) 2.31 - 2.10 (m, 9H) 2.06 - 1.52 (m, AcOH, 28H) 1.35 - 1.23 (m, 8H) 1.08 - 1.00 (m, 1H) 0.86 (dd, J = 11.5, 6.7 Hz, 6H) 0.76 - 0.70 (m, 6H).

[0156] Compound 102 Glu-Pro-Val-Pro-Gln-Ala-Lys-Val-Pro-Tyr (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 53 H 82 N 12 O 15 ; m / z: 564.3073 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 7.01 - 6.95 (m, 2H) 6.69 (d, J = 8.5 Hz, 2H) 4.40 (dd, J = 8.3, 6.4 Hz, 1H) 4.29 - 4.10 (m, 9H) 3.79 - 3.71 (m, 1H) 3.68 - 3.45 (m, 5H) 2.92 - 2.81 (m, 4H) 2.33 (t, J = 7.3 Hz, 2H) 2.26 (t, J = 7.7 Hz, 2H) 2.20 - 2.13 (m, 2H) 2.06 - 1.52 (m, AcOH, 25H) 1.33 - 1.21 (m, 5H) 0.86 (dd, J = 11.3, 6.7 Hz, 6H) 0.77 (dd, J = 17.6, 6.7 Hz, 6H).

[0157] Compound 103: Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Glu (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 126 N 22 O 21 ; m / z: 824.4799 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2O) δ 4.49 (dd, J = 9.6, 4.4 Hz, 1H) 4.45 (dd, J = 9.4, 4.9 Hz, 1H) 4.36 - 4.05 (m, 11H) 4.01 - 3.96 (m, 2H) 3.92 - 3.87 (m, 1H) 3.82 - 3.64 (m, 3H) 3.60 - 3.46 (m, 3H) 3.07 (t, J = 7.0 Hz, 2H) 2.88 - 2.83 (m, 6H) 2.29 - 2.09 (m, 9H) 1.99 - 1.46 (m, AcOH, 47H) 1.39 - 1.20 (m, 16H) 0.85 (dd, J = 14.2, 6.7 Hz, 6H) 0.80 (dd, J = 6.7, 3.7 Hz, 6H).

[0158] Compound 104: Lys - Glu - Pro - Val - Pro - Gln - Ala - Lys - Pro - Arg - Lys - Val - Ala - Ala - Asn (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 72 H 125 N 23 O 20 ; m / z: 408.9938 ([M + 4H] 4+ )、544.9891 ([M + 3H] 3+ )、816.9801 ([M + 2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ 4.49 (dd, J = 9.7, 4.4 Hz, 1H) 4.45 (dd, J = 9.4, 4.8 Hz, 1H) 4.34 - 4.10 (m, 11H) 3.96 (d, J = 7.6 Hz, 1H) 3.92 - 3.84 (m, 1H) 3.78 - 3.66 (m, 3H) 3.62 - 3.43 (m, 3H) 3.07 (t, J = 6.9 Hz, 2H) 2.90 - 2.82 (m, 6H) 2.63 (dd, J = 15.1, 4.9 Hz, 1H) 2.53 (dd, J = 15.1, 8.1 Hz, 1H) 2.30 - 2.11 (m, 7H) 2.03 - 1.42 (m, AcOH, 44H) 1.39 - 1.19 (m, 15H) 0.85 (dd, J = 14.0, 6.7 Hz, 6H) 0.80 (dd, J = 6.8, 3.0 Hz, 6H).

[0159] Compound 105: Lys-Gln-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 73 H 128 N 24 O 19 ; m / z: 412.2515 ([M+4H] 4+ )、549.3327 ([M+3H] 3+ )、823.4955 ([M+2H] 2+ ). 1 H NMR (600 MHz, D 2 O) δ4.53 (dd, J = 9.0, 5.0 Hz, 1H) 4.44 (dd, J = 9.4, 4.8 Hz, 1H) 4.34 (dd, J = 8.4, 6.0 Hz, 1H) 4.30 - 4.23 (m, 3H) 4.22 - 4.11 (m, 6H) 4.02 (dd, J = 8.4, 4.8 Hz, 1H) 3.96 (d, J = 7.6 Hz, 1H) 3.90 (t, J = 6.7 Hz, 1H) 3.80 - 3.63 (m, 3H) 3.60 - 3.42 (m, 3H) 3.07 (t, J = 6.9 Hz, 2H) 2.89 - 2.82 (m, 6H) 2.34 - 2.24 (m, 4H) 2.22 - 2.07 (m, 5H) 2.01 - 1.45 (m, AcOH, 50H) 1.39 - 1.20 (m, 15H) 0.85 (dd, J = 15.5, 6.7 Hz, 6H) 0.80 (dd, J = 6.8, 4.3 Hz, 6H).

[0160] Compound 106: Lys-Glu-Pro-Ile-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (acetate) High-resolution mass spectrometry (Orbitrap-HRMS), molecular formula: C 74 H 129 N 23 O 20 ; m / z: 416.0015 ([M+4H] 4+ )、554.3328 ([M+3H] 3+ )、830.9956 ([M+2H] 2+ ). 1 H NMR (600 MHz, D2 O) δ 4.50 (dd, J = 9.6, 4.4 Hz, 1H) 4.45 (dd, J = 9.3, 4.9 Hz, 1H) 4.36 - 4.22 (m, 4H) 4.22 - 4.10 (m, 6H) 4.02 (dd, J = 8.4, 4.9 Hz, 1H) 3.96 (d, J = 7.6 Hz, 1H) 3.92 - 3.84 (m, 1H) 3.82 - 3.74 (m, 1H) 3.73 - 3.63 (m, 2H) 3.61 - 3.41 (m, 3H) 3.07 (t, J = 6.9 Hz, 2H) 2.90 - 2.82 (m, 6H) 2.32 - 2.12 (m, 9H) 2.00 - 1.46 (m, AcOH, 46H) 1.43 - 1.05 (m, 17H) 0.84 (d, J = 6.8 Hz, 3H) 0.80 (dd, J = 6.8, 4.3 Hz, 6H) 0.75 (t, J = 7.4 Hz, 3H).

[0161] Compound 107: Val - Pro - Gln - Ala (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 18 H 31 N 5 O 6 ; m / z: 414.2341 ([M + 1H] + ). 1 H NMR (600 MHz, D 2 O) δ 4.29 (t, J = 7.6 Hz, 1H) 4.07 (dd, J = 8.5, 6.1 Hz, 1H) 4.01 - 3.91 (m, 2H) 3.61 - 3.53 (m, 1H) 3.46 - 3.41 (m, 1H) 2.24 - 2.10 (m, 4H) 1.95 - 1.69 (m, AcOH, 6H) 1.14 (d, J = 7.3 Hz, 3H) 0.91 (d, J = 7.0 Hz, 3H) 0.80 (d, J = 6.8 Hz, 3H).

[0162] Compound 108: Val - Pro - Gln - Ala - Lys (acetate) High - resolution mass spectrometry (Orbitrap - HRMS), molecular formula: C 24 H 43 N 7 O 7 ; m / z: 271.6681 ([M + 2H]2+), 542.3289 ([M + 1H] + ). 1 H NMR (600MHz, D 2 O)δ4.28(t,J=7.6Hz,1H)4.13-4.06(m,2H)3.99(d,J=5.5Hz,1H)3.94(dd,J =8.2,5.1Hz,1H)3.60-3.54(m,1H)3.46-3.41(m,1H)2.78(t,J=7.5Hz,2H)2. 21(t,J=7.6Hz,2H)2.17-2.09(m,2H)1.93-1.58(m,AcOH,11H)1.53-1.44(m ,3H)1.20(dd,J=9.7,7.5Hz,5H)0.91(d,J=6.9Hz,3H)0.80(d,J=6.9Hz,3H).

[0163] Example 2: Experiment showing that polypeptide compounds have a relieving effect on colitis Experimental animals: Wild-type AB species zebrafish bred by natural pair mating. Zebrafish were aged 3 days post-fertilization (dpf). All zebrafish were cultured in fish culture water at 28°C (water quality: 1 L of reverse osmosis water supplemented with 200 mg of instant sea salt, CaCO2 with conductivity of 450–550 μS / cm, pH of 6.5–8.5, and hardness of 50–100 mg / L). 3 The animals were kept in a laboratory animal license number: SYXK (Zhejiang) 2012-0171, and the breeding management met the requirements of the international AAALAC certification (certification number: 001458).

[0164] Testing Method: (1) Grouping: Polypeptide group: A mother solution of 20.0 mg / mL was prepared with ultrapure water and stored at -20°C. Positive control group: prednisone, white powder, lot number C10016501, Shanghai McLean Biotechnology Co., Ltd., stored at 4°C, a 15.0 mg / mL mother solution was prepared with DMSO and stored in aliquots at -20°C. Normal and model control groups. (2) Experimental method: 3dpf wild-type AB species zebrafish were randomly selected into 6-well plates, and 30 zebrafish were treated in each well (experimental group). Except for the normal control group, all other experimental groups were given water-soluble TNBS to establish a zebrafish intestinal mucosa injury model. After 2 days of treatment at 28°C, TNBS was removed, and water-soluble polypeptide compound (concentration see Table 4) and positive control prednisone 15.0μg / mL were given, respectively, while a normal control group (healthy group) and a model control group (intestinal mucosa injury group) were set up so that the volume of each well (experimental group) was 3mL. After continuing treatment at 28°C for 2 days, 10 zebrafish were randomly selected from each experimental group and photographed under a dissecting microscope, and analyzed using NIS-Elements D3.20 advanced image processing software to collect data, and the intestinal cavity area of ​​zebrafish was analyzed, and the statistical analysis results of this index were used to evaluate the effect of the sample on alleviating colitis. Statistical results were expressed as mean ± SE. Statistical analysis was performed using SPSS26.0 software, and p<0.05 indicated statistical significance. Experimental results: The results shown in Table 4 show that the polypeptide compound has an alleviating effect on colitis.

[0165] JPEG2025502306000009.jpg135142

[0166] Compared with the model control group, *p<0.05, **p<0.01, ***p<0.001. As can be seen from the data in Table 4, the polypeptide compound groups such as compounds 1, 4, 5, 6, 12, and 15 have significant statistical differences (p<0.05, p<0.01, p<0.001) compared with the model control group, and the effects are superior to those of the prednisone group. The experimental results show that the polypeptide compounds provided by the present application have an alleviating effect on colitis, specifically manifested as a significant alleviation of intestinal distension.

[0167] The concentration gradient of the test substance set in this experimental system was 250μg / mL, 500μg / mL, and 1000μg / mL, and by statistically examining the area of ​​the intestinal cavity of zebrafish after intervention in each group, it was found that most of the test substances with the effect of alleviating colitis had relatively obvious effects at a concentration of 1000μg / mL (p<0.05, p<0.01, p<0.001). On the other hand, when the test substance concentration continued to increase and intervention was performed, the death of zebrafish in the group was observed, so in the subsequent multiple activity evaluations, each test substance polypeptide compound was uniformly administered at 1000μg / mL and intervention was performed, and the results are summarized in Table 5.

[0168] JPEG2025502306000010.jpg198151

[0169] NOTE: The alleviation of intestinal lumen distension activity of zebrafish colitis by each compound was completed in a multi-batch test. For convenience of comparison, its anti-intestinal lumen distension activity was compared against the experimental model control group of the same batch. *p<0.05, **p<0.01, ***p<0.001, ND represents not tested, "-" represents no activity, "+" represents a certain alleviation effect of intestinal lumen distension, "#" represents all zebrafish died during the experiment, and "&" represents 13 zebrafish died during the experiment.

[0170] As can be seen from the data in Tables 4 and 5, the polypeptide group had significant statistical differences (p<0.05, p<0.01 or p<0.001) compared with the model control group, and the effect was superior to that of the prednisone group. Under these experimental conditions, compounds 1, 4-6, 9, 10, 12, 15, 25, 26, 29, 31, 34, 38, 48-51, 53-55, 57, 62, 63, 65-68, 70, 72, 75, 83, 85, 86, 88-90, 92-100, and 103-106 all had significant alleviating effects on colitis, specifically intestinal inflammation. This was manifested as a relaxation of intestinal distension (p<0.05), and compounds 7, 8, 11, 14, 16, 17, 19, 21-24, 27, 28, 30, 32, 33, 36, 37, 39-42, 46, 47, 52, 58, 59, 64, 69, 71, 74, 76, 78-82, 84, 87, 91 and 102 had a certain relaxation effect on intestinal distension.

[0171] Example 3: Evaluation of therapeutic effects of polypeptide compounds on TNBS-induced acute inflammatory bowel disease (UC) model in SD rats Objective: To evaluate the therapeutic effects of polypeptide compounds on TNBS-induced acute inflammatory bowel disease model in SD rats.

[0172] Materials and Methods: In this experiment, a single enema intervention was performed using trinitrobenzene sulfonic acid (TNBS) in experimental male SD rats to establish a rat ulcerative colitis model. Trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats is a cytokine-induced immune response secreted by Thl-type cells, and the colon of the model control group animals showed obvious atrophy and thickening of the intestinal wall, the weight-to-length ratio of the colon was significantly increased, crack-like ulcer lesions were observed on the surface of the intestinal wall mucosa, typical granulomas were observed in the submucosa and muscular layer, accompanied by the infiltration of inflammatory cells mainly composed of lymphocytes and plasma cells inside, and at the same time, small blood vessels and fastening tissue proliferation (fibroblasts) were evident, and destruction of the crypt structure and bleeding were observed around the ulcer lesion. This model is easy to prepare, has good reproducibility, and is an experimental animal model that is widely applied to the evaluation of therapeutic drugs for inflammatory bowel disease. On the first day of the experiment, the experimental animals (male SD rats) were randomly divided into 6 groups according to the weight parameters, including normal control group, model control group, positive drug mesalazine treatment group, low dose compound 1 treatment group, high dose compound 1 treatment group, low dose compound 6 treatment group, high dose compound 6 treatment group and compound 12 treatment group, with 10 animals per group. On the day of grouping (D0), except for the normal control group administered with the solvent, all the animals in each experimental group were administered with TNBS ethanol solution by enema for model induction, and the treatment of the test article and positive control drug was started from the day after model induction.The therapeutic doses of compound 1 were 3.0 mg / kg and 6.0 mg / kg, compound 6 were 1.4 mg / kg and 2.8 mg / kg, compound 12 was 0.8 mg / kg, and the positive control drug mesalazine was 30.0 mg / kg. All were administered by enema once a day for 14 consecutive days. During the treatment period (D1 to D14) of the experiment, the body weight and general clinical observation indicators (eating, drinking, activity level, defecation, etc.) of the animals in each experimental group were recorded. (including but not limited to) were dynamically collected, and at the same time, the degree of weight loss, morphology and properties of feces, and fecal blood in the animals of each experimental group after TNBS induction were scored based on the ulcerative colitis disease activity-related scoring criteria, and the ulcerative colitis disease activity (DAI) was calculated once a day for 14 consecutive days. At the end of the experiment, the colon tissues of the animals of each experimental group were collected, the length of the colon was measured, and after weighing, non-necropsy images were collected, and then the intestinal wall was cut longitudinally and necropsy images were collected. Based on the "Colon Macroscopic Morphological Expression Scoring Criteria", the colon adhesions, colon ulcers, and macroscopic damage of inflammation of the animals of each experimental group were observed and scored. Ulcer images were collected under a stereomicroscope, the area of ​​colon ulcer lesions was calculated, and then normal fixation was performed. Based on the statistical analysis results of various pharmacodynamic test indexes, the therapeutic effect of the test polypeptide compound in the ulcerative colitis disease model with the set treatment plan was evaluated.

[0173] Results and conclusions: In this experimental research system, the animals in the model control group showed obvious disease characteristics of ulcerative colitis, including inhibition of weight gain, loose and rare stools, a significant increase in the DAI score of ulcerative colitis disease activity, macroscopically observable colon atrophy, and typical ulcer lesions and colonic fused ulcer lesions. Test compound 1 had obvious improving effect on the inhibition of weight gain of the model animals in the established treatment plan, and the degree of improvement had a statistical difference (P<0.05) compared with the degree of change in animal weight of the model control group during the same period, while test compounds 6 and 12 showed no obvious improvement on the therapeutic effect of inhibition of weight gain of the model animals.

[0174] JPEG2025502306000011.jpg107162

[0175] Note: All data were analyzed statistically using mean ± standard deviation (SD). * P < 0.05, ** P < 0.01, *** P<0.001, **** P<0.0001 represents the statistical analysis results of the model control group and the normal control group; # P < 0.05, ## P<0.01 represents the statistical analysis result between the test polypeptide compound treated animals and the model control group.

[0176] The DAI scoring results during the experimental period showed that test compounds 1, 6 and 12 had obvious ameliorative effects on the progression of ulcerative colitis disease in the model animals under the established treatment regimen, and the fecal lesion characteristics and weight loss response of the corresponding treatment group animals were all significantly alleviated, and the average DAI scores all decreased, with obvious statistical differences (P<0.05) compared with the model control group during the same period. The improvement on the therapeutic effect of compound 1 was the most obvious, while the therapeutic effects of compounds 1 and 6 were obviously dose-dependent.

[0177] JPEG2025502306000012.jpg71166

[0178] Note: All data were analyzed statistically using mean ± standard deviation (SD). * P < 0.05, ** P < 0.01, *** P<0.001, **** P<0.0001 represents the statistical analysis results of the model control group and the normal control group; # P < 0.05, ## P < 0.01, ### P<0.001, #### P<0.0001 represents the statistical analysis result of the test polypeptide compound treated animals and the model control group. + P < 0.05, ++ P < 0.01, +++ P<0.001, ++++P<0.0001 represents the statistical analysis result between compound 1 or 6 dose groups.

[0179] The results of gross dissection and colonic tissue damage scoring at the end of the experiment showed that test compounds 1, 6 and 12 had obvious therapeutic effects on TNBS-induced colonic gross damage status (colon adhesion, ulcer and inflammation), the abnormal increase process of colonic ulcer lesion area and colon weight / length ratio, and the degree of improvement was statistically different (P<0.05) compared with the model control group during the same period, with compound 1 having the most obvious therapeutic effect and at the same time, the therapeutic effect had obvious dose-dependency.

[0180] JPEG2025502306000013.jpg65166

[0181] Note: All data were analyzed statistically using mean ± standard deviation (SD). * P < 0.05, ** P < 0.01, *** P<0.001, **** P<0.0001 represents the statistical analysis results of the model control group and the normal control group; # P < 0.05, ## P < 0.01, ### P<0.001, #### P<0.0001 represents the statistical analysis result of the test polypeptide compound treated animals and the model control group. + P < 0.05, ++ P < 0.01, +++ P<0.001, ++++ P<0.0001 represents the statistical analysis result between compound 1 or 6 dose groups.

[0182] JPEG2025502306000014.jpg68170

[0183] Note: All data were analyzed statistically using mean ± standard deviation (SD). * P < 0.05, ** P < 0.01, *** P<0.001, ****P<0.0001 represents the statistical analysis results of the model control group and the normal control group; # P < 0.05, ## P < 0.01, ### P<0.001, #### P<0.0001 represents the statistical analysis result of the test polypeptide compound treated animals and the model control group. + P < 0.05, ++ P < 0.01, +++ P<0.001, ++++ P<0.0001 represents the statistical analysis result between compound 1 or 6 dose groups.

[0184] In this study, TNBS was used to perform enema intervention in male SD rats to induce colonic lesions and establish an ulcerative colitis model that meets the clinical onset characteristics. The treatment with test compounds 1, 6, 12 and the positive control drug mesalazine was started the day after the model induction. The therapeutic effect of the test product on the TNBS-induced SD rat ulcerative colitis model was evaluated by monitoring the changes in the body weight of the experimental animals, the score of ulcerative colitis disease activity DAI, the score of macroscopic damage expression of the colon (colonic adhesion, ulcer and inflammatory response), the ulcer area of ​​the colon tissue and the colon weight / length ratio, etc., during the treatment cycle (D1-D14). The results showed the following.

[0185] 1) The experimental animals showed obvious ulcerative colitis disease after TNBS induction, mainly including significant weight loss, significant increase in ulcerative colitis disease activity score (DAI score), significant increase in colon adhesion and ulcer score, increase in ulcer area of ​​colon tissue, and significant increase in colon weight / length ratio, suggesting that the rat ulcerative colitis model was successfully established and suitable for pharmacodynamic study in this experiment. 2) Test compound 1 had a clear improving effect on the weight loss of the model animals under the established treatment plan, and the degree of improvement had a statistical difference (P<0.05) compared with the model control group during the same period, while test compounds 6, 12 and the positive control drug mesalazine did not show a clear weight improving effect. 3) Test compounds 1, 6 and 12 had obvious ameliorative effects on the disease process of ulcerative colitis in model animals under the established treatment regimen, and the DAI scores all showed a significant decrease compared with the model control group during the same period, with the therapeutic effect of test compound 1 being the most obvious, and at the same time, the ameliorative and therapeutic effects of test compounds 1 and 6 had obvious dose-dependence, while the positive control drug mesalazine had no obvious effect on the disease symptoms of ulcerative colitis in model animals.

[0186] 4) Test compounds 1, 6 and 12 had obvious therapeutic effects on the macroscopic damage expression of the colon of the model animals under the established treatment schedule. Compared with the model control group during the same period, the colon adhesion score, colon ulcer and inflammation score, and the area of ​​ulcer lesion in the colon tissue were all significantly reduced, and the degree of improvement was statistically significant (P<0.05). The therapeutic effect of test compound 1 was the most obvious, and the improvement and therapeutic effect had obvious dose-dependency. 5) Test compounds 1, 6 and 12 had obvious improving effects on the colon atrophy process of the model animals in the established treatment regimen, and the colon weight / length ratio was significantly reduced (P<0.05) compared with the model control group in the same period. This study established a rat ulcerative colitis model that met the clinical onset characteristics, and the results of efficacy evaluation in this model showed that test compounds 1, 6 and 12 all had significant therapeutic effects.

[0187] Example 4: Study of the effect of polypeptide compounds on the in vitro proliferation of CaCo-2 cells The following cell lines were used to study the in vitro propagation of polypeptide compounds:

[0188] JPEG2025502306000015.jpg23145

[0189] Testing Method: The cells were resuscitated and maintained according to the culture conditions shown in Table 10. Day 1 (cell seeding): Cells in logarithmic growth phase were collected and resuspended, then counted using a cell counter to detect activity. The cell suspension was diluted according to the requirement of seeding density, and 90 μL of cell suspension was added to each well of a 96-well plate (cell seeding density was adjusted based on historical data or density optimization experiments). At the same time of seeding, each cell was seeded into three parallel wells as T0 plate. All 96-well plates were placed in a 37°C, 5% CO2 constant temperature incubator overnight.

[0190] Day 2 (liquid exchange): According to the platemap, the medium corresponding to the serum concentration was exchanged at 90 μL / well. Day 2: The T0 plate was read and the compounds to be measured were treated. 10 μL of medium was added to each well of the T0 plate to replenish the total volume to 100 μL. 50 μL of CellTiter-Glo® reagent was added to each well. The cells were mixed and shaken for 5 minutes to fully dissolve. To stabilize the luminescence signal, the cells were incubated at room temperature for 10 minutes (Note: temperature, cell density and edge effect all cause non-uniformity of the luminescence signal). The fluorescent signal was detected using an EnVision Multi Label Reader. The compounds to be measured were diluted according to the corresponding molecular weight settings: C1 = 91.08 μM, C2 = 9.108 μM, C3 = 0.9108 μM. Cisplatin was diluted as shown in Table 11 to prepare 10× compound working solution. 10 μL of working solution (10×) was added to each well, and the final volume of each well of all plates was 100 μL. The cells were cultured in an incubator at 37°C and 5% CO2.

[0191] On the fifth day, the compound to be measured was treated for 72 hours (plate reading). The conditions of the treated and control groups were observed under a microscope to see if they were normal. 50 μL of CTG reagent was added to each well. The wells were mixed on a shaker for 5 minutes to ensure that the cells were sufficiently dissolved. The wells were incubated at room temperature for 10 minutes to stabilize the luminescence signal. The fluorescent signal was read using an EnVision Multi Label Reader.

[0192] Table 11 Cisplatin concentration after dilution JPEG2025502306000016.jpg26164

[0193] Cell viability (%)=Lum 測定される化合物 / Lum 溶媒対照 ×100% Experimental Results: The statistical results of the proliferation-promoting activity of the selected polypeptide compounds are shown in Table 12.

[0194] JPEG2025502306000017.jpg3388

[0195] The administration concentration gradient of the test substance set in this experimental system was 0.88% FBS as a reference, and diluted C1=91.08μM, C2=9.108μM, and C3=0.9108μM. The experimental results showed that the polypeptide compound 1 of the present application has the activity of promoting Caco-2 cell proliferation, specifically manifested as an increase in cell viability after intervention.

[0196] In conclusion, the above-mentioned polypeptide compound of the present invention has a shorter peptide chain, and is absorbed faster and better.The experimental results show that the polypeptide compound provided by the present application can alleviate the intestinal lumen expansion activity of zebrafish colitis, and has a significant therapeutic effect in rat acute inflammatory bowel disease model test.The above-mentioned polypeptide compound of the present invention has a significant alleviating effect on colitis, and can be used to manufacture drugs for treating enteritis, especially drugs for ulcerative colitis.

[0197] Although the present invention discloses the above examples, the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the present invention are equivalent substitutions, and all fall within the protection scope of the present invention.

Claims

1. A compound according to formula (I) or a physiologically acceptable salt thereof, The compound of formula (I) is H-X ａ -Z １ -Z ２ -Z ３ -Z ４ -X ｂ -OH (I) -. Where: Z １ is Pro, Ala, Gly, D-Pro or deleted, Z ２ is Val, Ala, D-Val, Ile or deleted, Z ３ is Pro, Ala, Gly, D-Pro or deleted, Z ４ is Gln, Ala, Glu, Ile, D-Gln or deleted, As a condition, Z １ , Z ２ , Z ３ and Z ４ Two or fewer of them are deleted, X ａ is a sequence containing 0 to 10 amino acid residues, X ｂ is a sequence containing 0 to 9 amino acid residues, The compound or a physiologically acceptable salt thereof.

2. Z １ , Z ２ , Z ３ and Z ４ Two of them are deleted or Z １ and Z ２ is deleted, or Z ３ and Z ４ is deleted, or Z １ , Z ２ , Z ３ and Z ４ One of the genes is deleted, or Z １ is deleted, or Z ４ is deleted, or Z １ , Z ２ , Z ３ and Z ４ 0 of the digits are deleted.

2. A compound according to claim 1 or a physiologically acceptable salt thereof.

3. Z １ , Z ２ , Z ３ and Z ４ 0 of the digits are deleted.

2. A compound according to claim 1 or a physiologically acceptable salt thereof.

4. Z １ Pro, Z ２ Val, Z ３ Pro and Z ４ is Gln, or Z １ D-Pro, Z ２ Val, Z ３ Pro and Z ４ is Gln, or Z １ Pro, Z ２ Val, Z ３ is Ala, and Z ４ is Gln, or Z １ Pro, Z ２ Ile, Z ３ Pro and Z ４ is Gln, or Z １ Pro, Z ２ Val, Z ３ Pro and Z ４ is deleted, or Z １ Pro, Z ２ Ala, Z ３ Pro and Z ４ is Gln, or Z １ is Gly, Z ２ Val, Z ３ Pro and Z ４ is Gln, or Z １ Pro, Z ２ Val, Z ３ is Gly, and Z ４ is Gln, or Z １ Ala, Z ２ Val, Z ３ Pro and Z ４ is Gln, or Z １ Pro, Z ２ Val, Z ３ Pro and Z ４ is Glu, or Z １ Pro, Z ２ Val, Z ３ D-Pro and Z ４ is Gln, or Z １ Pro, Z ２ Val, Z ３ Pro and Z ４ is D-Gln, 2. A compound according to claim 1 or a physiologically acceptable salt thereof.

5. Z １ Pro, Z ２ Val, Z ３ Pro and Z ４ is Gln; 2. A compound according to claim 1 or a physiologically acceptable salt thereof.

6. X ａ Is X ａ１０ -X ａ９ -X ａ８ -X ａ７ -X ａ６ -X ａ５ -X ａ４ -X ａ３ -X ａ２ -X ａ１ -*, where * is Z １ -Z ２ -Z ３ -Z ４ represents the position of coupling to X ａ１０ is Gly or is deleted, X ａ９ is Gly, Pro, Ser or is deleted, X ａ８ is Pro, Glu, Ser or is deleted, X ａ７ is Arg, Glu, Thr, Ser or is deleted, X ａ６ is Lys, Thr, Ala, Asp, Glu, Arg, Ser or is deleted, X ａ５ is Asp, Ala, Val, Arg, Phe, Ile, Pro, Lys, Glu or is deleted, X ａ４ is Val, Phe, Pro, Pyro-Glu, Lys, Leu, Ile, Ala, Asp or is deleted, X ａ３ is Tyr, Leu, Pro, Asp, Arg, Glu, Lys, Tys, Val, Ile or is deleted, X ａ２ is D-Lys, Lys, Ala, Arg, Val, Glu, Tyr or is deleted, and X ａ１ is Glu, Ala, D-Glu, Tyr, Gln, Asp, Asn or deleted, 6. A compound or a physiologically acceptable salt thereof according to any one of claims 1 to 5.

7. X ａ Is X ａａ -X ａ２ -X ａ１ -*, where * is Z １ -Z ２ -Z ３ -Z ４ represents the position of linkage to ａ２ -X ａ１ is Lys-Glu-*, Arg-Glu-*, Val-Tyr-*, Glu-Glu-*, Lys-Gln-*, Lys-D-Glu-* or Tyr-Glu-*, and X is ａａ Is X ａ１０ -X ａ９ -X ａ８ -X ａ７ -X ａ６ -X ａ５ -X ａ４ -X ａ３ -, where X ａ１０ is Gly or deleted, and X ａ９ is Gly, Pro, Ser or is deleted, and X ａ８ is Pro, Glu, Ser or is deleted, and X ａ７ is Arg, Glu, Thr, Ser or is deleted, and X ａ６ is Lys, Thr, Ala, Asp, Glu, Arg, Ser or is deleted, and X ａ５ is Asp, Ala, Val, Arg, Phe, Ile, Pro, Lys, Glu or is deleted, ａ４ is Val, Phe, Pro, Pyro-Glu, Lys, Leu, Ile, Ala, Asp or is deleted, and X ａ３ is Tyr, Leu, Pro, Asp, Arg, Glu, Lys, Tys, Val, Ile or deleted, 7. A compound according to claim 6 or a physiologically acceptable salt thereof.

8. X ａａ is Arg-Lys-Asp-Val-Tyr-, Gly-Pro-Glu-Thr-Ala-Phe-Leu-, Val-Pro-Pro-, Pyro-Glu-Leu-, Arg-Lys-Asp-, Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-, Ser-Ser-Glu-Asp-Ile-Lys-Glu-, Ser-Ser-Glu-Asp-Ile-Lys-, Val-Pro-Tys-, Pro-Ala-Tys-, Arg-Lys-Asp-Val-, Ser-Ser-Glu-Asp-Ile- or deleted, wherein the rightmost hyphen - is -X ａ２ -X ａ１ Representing a connection with 8. A compound according to claim 7 or a physiologically acceptable salt thereof.

9. X ａ Is X ａａ -X ａ２ -X ａ１ -*, where * is Z １ -Z ２ -Z ３ -Z ４ represents the position of linkage to ａ２ -X ａ１ is Lys-Glu-*, and X ａａ is as defined above, 8. A compound according to claim 7 or a physiologically acceptable salt thereof.

10. X ａ are Glu-*, Ala-*, D-Glu-*, Asp-*, Asn-*, Lys-Glu-*, D-Lys-Glu-*, Ala-G lu-*, Lys-Gln-*, Lys-D-Glu-*, Lys-Ala-*, Arg-Lys-Asp-Val-Tyr-Lys -Glu-*, Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Glu-*, Val-Pro-Pro-Lys -Glu-*, Pyro-Glu-Leu-Lys-Glu-*, Arg-Lys-Asp-Val-Tyr-*, Gly-Pro-G lu-Thr-Ala-Phe-Leu-Arg-Lys-Glu-*, Ser-Ser-Glu-Asp-Ile-Lys-Glu-LysGlu-*, Ser-Ser-Glu-Asp-Ile-Lys-Glu-Glu-*, Val-Pro-Tys-Lys-Glu-*, Pro-Ala-Tys-Lys-Glu-*, Arg-Lys-Asp-Val-Tyr-Glu-*, Ser-Ser-Glu-Asp-Ile-Lys-Glu-* or deleted, wherein * represents the position of linkage to Z1-Z2-Z3-Z4, 7. A compound according to claim 6 or a physiologically acceptable salt thereof.

11. X ｂ is **-X ｂ１ -X ｂ２ -X ｂ３ -X ｂ４ -X ｂ５ -X ｂ６ -X ｂ７ -X ｂ８ -X ｂ９ where ** is Z １ -Z ２ -Z ３ -Z ４ represents the position of coupling to X ｂ１ is Ala, D-Ala or deleted, X ｂ２ is Lys, Ala, D-Lys, Arg or is deleted, X ｂ３ is Pro, Gly, D-Pro, Ser, Val, Ala or is deleted, X ｂ４ is Arg, Ala, Ser, Pro, D-Arg or is deleted, X ｂ５ is Lys, Ala, D-Lys, Glu, Tyr or is deleted, X ｂ６ is Val, Asp, D-Val, Ala or is deleted, X ｂ７ is Ala, D-Ala, Ile or deleted, X ｂ８ is Ala, D-Ala, Lys or is deleted, and X ｂ９ is Gln, Ala, Glu, Asn, D-Gln or deleted, 11. A compound or a physiologically acceptable salt thereof according to any one of claims 1 to 10.

12. X ｂ is **-X ｂ１ -X ｂ２ -X ｂ３ -X ｂ４ -X ｂ５ -X ｂ６ -X ｂ７ -X ｂ８ -X ｂ９ where ** is Z １ -Z ２ -Z ３ -Z ４ represents the position of coupling to X ｂ１ is Ala or D-Ala, X ｂ２ is Lys, Ala or D-Lys, X ｂ３ is Pro, Gly, or Ala, X ｂ４ is Arg or D-Arg, X ｂ５ is Lys or is deleted, X ｂ６ is Val, D-Val, Ala or deleted, X ｂ７ is Ala or deleted, X ｂ８ is Ala or deleted, and X ｂ９ is Gln, Asn, D-Gln or deleted, 12. A compound or a physiologically acceptable salt thereof according to claim 11.

13. X ｂ is **-X ｂ１ -X ｂ２ -X ｂｂ where ** is Z １ -Z ２ -Z ３ -Z ４ represents the position of linkage to ｂ１ -X ｂ２ - is **-Ala-Lys-, **-Ala-Lys-, **-Ala-D-Lys-, **-Ala-Ala- or **-D-Ala-Lys-, and X ｂｂ Is X ｂ３ -X ｂ４ -X ｂ５ -X ｂ６ -X ｂ７ -X ｂ８ -X ｂ９ where X ｂ３ is Pro, Gly, D-Pro, Ser, Val, Ala or is deleted, and X ｂ４ is Arg, Ala, Ser, Pro, D-Arg or deleted, X ｂ５ is Lys, Ala, D-Lys, Glu, Tyr or is deleted, and X ｂ６ is Val, Asp, D-Val, Ala or deleted, and X ｂ７ is Ala, D-Ala, Ile or deleted, and X ｂ８ is Ala, D-Ala, Lys or deleted, and X ｂ９ is Gln, Ala, Glu, Asn, D-Gln or is deleted, or X ｂ３ is Pro, Gly, or Ala; ｂ４ is Arg or D-Arg, X ｂ５ is Lys or deleted, and X ｂ６ is Val, D-Val, Ala or deleted, and X ｂ７ is Ala or deleted, and X ｂ８ is Ala or deleted, and X ｂ９ is Gln, Asn, D-Gln or deleted, 13. A compound or a physiologically acceptable salt thereof according to claim 11 or 12.

14. X ｂｂ Pro-Arg-Lys-Val, Pro-Arg-Lys, Pro-Arg, Ala-Gln, Ala-Ala, Pro, Lys-Val, Val-Pro-Tyr, Arg-Lys, Val-Ala, Pro-Arg-Lys-Val-Ala, Lys-Val-Ala, Pro-Arg-Lys-Val-Ala, Lys-Val-Ala-Ala-Gln, Pro-Arg-L You are Val-Ala-Ala-Gln, Pro-Ala-Lys-Val-Ala-Ala-Gln, Pro-Arg-Ala-Val-Ala-Ala-Gln, Pro-Arg-Lys-Val-Ala-Ala-Ala-Gln, Gly-Arg-Lys-Val-Ala-Ala-Gln, D-Pro-Arg-Lys-Val-Ala-Ala-Gln, Pro-Arg-D-Lys-Val-Ala-Ala-Gln -Al-Al--Gln、-Pro-Arg-Lys----D-Aln-Al-Gln、-2o-Ag-*s---------------------- -Ile-Lys-Glu、-Pro-As-Lys----Al-Al-Asn、----------------------- a- -Gln、-Pro-D-Arg-Ly-&--Al-Al---n、-2o-Arg-*s------------.----------- ｂ１ -X ｂ２ ととますます 14. A compound according to claim 13 or a physiologically acceptable salt thereof.

15. X ｂ is **-X ｂ１ -X ｂ２ -X ｂｂ where ** is Z １ -Z ２ -Z ３ -Z ４ represents the position of linkage to ｂ１ -X ｂ２ - is **-Ala-Lys-, X ｂｂ is as defined above, 14. A compound according to claim 13 or a physiologically acceptable salt thereof.

16. X ｂ は**-Ala-、**-Ala-Lys、**-Ala--D-Lys、**-Ala-、**-D-Ala-Lys、**-Ala-Arg、**-Ala-Lys-Pro-Arg-Lys-Val、**-Ala-Lys-Pro-Arg-Lys、**-Ala-Lys-Pro-Arg、**-Val-Ala-Ala-、**-Ala-Lys-Pro-Arg、**-Val-Ala-Ala-、**-Pro-Arg-Lys-Val、**-Ala-Lys-Pro-Arg、**-Pro-Arg-Lys-Val、**-Ala-Lys-Val-Pro-Tyr、**-Lys-P Arg-Lys, ****Arg-Lys-Val-Ala, ***Ala-Lys-Pro-Arg-Lys-Val-Ala, ***Pro-Arg-Lys-Val-Ala-Ala-Gln, ***Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln, ***Ala-Ala-Pro-Arg-Lys-Val-Ala-Ala-Gln, ***Ala-Lys-Pro-Ala-Lys-Val-Ala-Ala-Gln, ***Ala-Lys-Pro-Ala-Lys-Val-Ala-Ala-Gln, ***Ala-Lys-Pro-Arg-Ala-Val-Ala-Ala-Gln, ***Ala-Lys-Pro-Ala-Lys-Val-Ala-Ala-Gln, ***Ala-Lys-Pro-Arg-Ala-Val-Ala-Ala-Gln - rg-Lys-Vl-Al-Ala-Gln、**-Ala-Lys-D-Pro-Ar-Lms-**-Als-*** - rg-Lys-Val-D-Al-Ala-Gln、**-Ala-Lys-Pro-Ar-Lys-Al-Als-*** - G - -**-D-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln, **-Ala-Lys-Pro-D-Arg-Lys-Val-Ala-Ala-Gln, **-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln, **-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-D-Gln or deletion, where ** is Z, １ -Z ２ -Z ３ -Z ４ represents the position where the 2. A compound according to claim 1 or a physiologically acceptable salt thereof.

17. The compound is Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 1), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys (compound 2), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (compound 3), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 4), Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 5), Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 6), Lys-Glu-Pro-Val (compound 7), Val-Ala-Ala-Gln (compound 8), Glu-Pro-Val-Pro (compound 9), Lys-Pro-Arg-Lys (compound 10), Ala-Lys-Pro-Arg (compound 11), Pro-Val-Pro-Gln (compound 12), Val-Pro-Gln-Ala (Compound 13), Pro-Gln-Ala-Lys (Compound 14), Arg-Lys-Val-Ala (Compound 15), Lys-Val-Ala-Ala (Compound 16), Gln-Ala-Lys-Pro (Compound 17), Pro-Arg-Lys-Val (Compound 18), Ala-Glu-Pro-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 19), Lys-Ala-Pro-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 20), Lys-Glu-Ala-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 21), Lys-Glu-Pro-Val-Ala-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 22), Lys-Glu-Pro-Val-Pro-Ala-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 23), Lys-Glu-Pro-Val-Pro-Gln-Ala-Ala-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 24), Lys-Glu-Pro-Ala-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 25), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-A la-Arg-Lys-Val-Ala-Ala-Gln (compound 26), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-P ro-Ala-Lys-Val-Ala-Ala-Gln (compound 27), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-P ro-Arg-Ala-Val-Ala-Ala-Gln (compound 28), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Ala-Ala-Ala-Gln (compound 29), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Ala (compound 30), Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 31), Lys-Glu-Pro-Val-Gly-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 32), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-G ly-Arg-Lys-Val-Ala-Ala-Gln (compound 33), Lys-Glu-Pro-Val-Gly-Gln-Ala-Lys-G ly-Arg-Lys-Val-Ala-Ala-Gln (compound 34), Lys-Glu-Gly-Val-Gly-Gln-Ala-Lys-G ly-Arg-Lys-Val-Ala-Ala-Gln (compound 35), Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-G ly-Arg-Lys-Val-Ala-Ala-Gln (compound 36), Lys-Glu-Gly-Val-Gly-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 37), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys (Compound 38), Pro-Val-Pro-Gln-Ala (Compound 39), Pro-Val-Pro-Glu-Ala (Compound 40), Pro-Val-Pro-Ile-Ala (Compound 41), Pro-Val-Pro-Ala (compound 42), Glu-Pro-Val-Pro-Gln-Ala (Compound 43), Pro-Val-Pro-Gln-Ala-Lys (Compound 44), Glu-Pro-Val-Pro-Gln-Ala-Arg (Compound 45), Ala-Pro-Val-Pro-Gln-Ala-Lys (Compound 46), Glu-Pro-Val-Pro-Ala-Ala-Lys (Compound 47), Glu-Pro-Val-Pro-Gln-Ala-Ala (Compound 48), Asp-Pro-Val-Pro-Gln-Ala-Lys (Compound 49), Asn-Pro-Val-Pro-Gln-Ala-Lys (Compound 50), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala (Compound 51), Glu-Pro-Ala-Pro-Gln-Ala-Lys (Compound 52), Glu-Ala-Val-Pro-Gln-Ala-Lys (Compound 53), Glu-Pro-Val-Ala-Gln-Ala-Lys (Compound 54), Glu-Pro-Val-Pro-Glu-Ala-Lys (Compound 55), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val (Compound 56), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (Compound 57), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro (Compound 58), Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (Compound 59), Pro-Val-Pro-Gln-Ala-Lys-Pro (Compound 60), D-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 61), Lys-D-Glu-Pro-Val-Pro-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 62), Lys-Glu-D-Pro-Val-Pro-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 63), Lys-Glu-Pro-D-Val-Pro-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 64), Lys-Glu-Pro-Val-D-Pro-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 65), Lys-Glu-Pro-Val-Pro-D-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 66), Lys-Glu-Pro-Val-Pro-Gln-D-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 67), Lys-Glu-Pro-Val-Pro-Gln-Ala-D-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 68), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-D- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 69), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-D-Arg-Lys-Val-Ala-Ala-Gln (compound 70), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-Arg-D-Lys-Val-Ala-Ala-Gln (compound 71), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-Arg-Lys-D-Val-Ala-Ala-Gln (compound 72), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-Arg-Lys-Val-D-Ala-Ala-Gln (compound 73), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-Arg-Lys-Val-Ala-D-Ala-Gln (compound 74), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-Arg-Lys-Val-Ala-Ala-D-Gln (compound 75), Glu-Gly-Val-Pro-Gln-Ala-Lys (Compound 76), Glu-Pro-Val-Gly-Gln-Ala-Lys (Compound 77), D-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 78), Glu-D-Pro-Val-Pro-Gln-Ala-Lys (Compound 79), Glu-Pro-D-Val-Pro-Gln-Ala-Lys (Compound 80), Glu-Pro-Val-D-Pro-Gln-Ala-Lys (Compound 81), Glu-Pro-Val-Pro-D-Gln-Ala-Lys (Compound 82), Glu-Pro-Val-Pro-Gln-D-Ala-Lys (Compound 83), Glu-Pro-Val-Pro-Gln-Ala-D-Lys (Compound 84), Lys-Glu-Pro-Val-Pro (Compound 85), Glu-Pro-Val-Pro-Gln (Compound 86), Lys-Glu-Pro-Val-Pro-Gln (Compound 87), Val-Pro-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala -Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 88), Pyro-Glu-Leu-Lys-Glu-Pro-Val-Pro-Gln-Ala -Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 89), Pro-Al-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Al-Lys-Pro-Arg-Lys-Val-Al-Ala-Gln (Compound 90), Arg-Lys-Asp-Val-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Al-Lys-Pro-Arg-Lys-Val-Al-Al-Gln (Compound 91), Arg-Lys-Asp-Val-Tyr-Lys-Glu-Pro-Val-Pro-Glu-Al-Lys (Compound 92), Arg-Lys-Asp-Val-Tyr-Glu-Pro-Val-Pro-Gln-Ala-Ly3-2 Arg-Lys-Asp-Val-Tyr-Pro-Val-Pro-Gln(compound94), Gly-Pro-Glu-Thr-Al-Phe-Leu-Arg-Lys-Glu-Pro-Val-Pro-Gln-Al-Lys-Pro-Arg-Lys-Val-Al-Ala-Gln (Compound 95), Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Glu-Po-Val-Pro-Gln-Ala-Lms-(Compound9660 Ser-Ser-Glu-Asp-Ile-Lys-Glu-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 97), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Glu-Pro-Val-Pro-Glu-Ala-Lys (Compound 98), Ser-Ser-Glu-Asp--le-Lys-Glu-Pro-Val-Pro-Gln(compound99), Zal-Pro-Pro-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-2o-Ar-Vl-Al-10000000 Glu-Pro-Val-Pro-Glu-Al-Lys-Ser-Ser-Glu-Asp-Ile-Lys-Glu (Compound 101), - Lysine-Glue-Pro-Val-Pro-Glue-Al-Lysine-Pro-Arg-Lysine-Val-Al-Al-Glue (Compound 103), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Asn (compound 104), Lys-Gln-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 105), Lys-Glu-Pro-Ile-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 106), Val-Pro-Gln-Ala (compound 107), or Val-Pro-Gln-Ala-Lys (compound 108), 2. A compound according to claim 1 or a physiologically acceptable salt thereof.

18. The compound is Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 1), Lys-Glu-D-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 63), Gly-Pro-Glu-Thr-Ala-Phe-Leu-Arg-Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 96), Val-Pro-Pro-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 100), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Asn (compound 104), Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 6), Pro-Val-Pro-Gln (compound 12), Glu-Pro-Val-Ala-Gln-Ala-Lys (compound 54), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg (compound 57), Lys-Glu-Pro-Val-Pro-Gln-Ala-D-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 68), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-D-Val-Ala-Ala-Gln (compound 72), Pyro-Glu-Leu-Lys-Glu-Pro-Val-Pro-Gln-Ala -Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 89), Arg-Lys-Asp-Val-Tyr-Lys-Glu-P ro-Val-Pro-Gln-Ala-Lys (compound 92), Arg-Lys-Asp-Val-Tyr-Pro-Val-Pro-Gln (Compound 94), Gly-Pro-Glu-Thr-Ala-Phe- Leu-Arg-Lys-Glu-Pro-Val-P ro-Gln-Ala-Lys-Pro-Arg-Ly s-Val-Ala-Ala-Gln (compound 95), Ser-Ser-Glu-Asp-Ile-Lys -Glu-Lys-Glu-Pro-Val-Pro -Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 97), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Glu -Pro-Val-Pro-Gln-Ala-Lys (Compound 98), Lys-Gln-Pro-Val-Pro-Gln-Ala-Lys-Pr o-Arg-Lys-Val-Ala-Ala-Gln (compound 105), Lys-Glu-Pro-Ile-Pro-Gln-Ala-Lys-Pr o-Arg-Lys-Val-Ala-Ala-Gln (compound 106), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys (Compound 4), Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 5), Glu-Pro-Val-Pro (compound 9), Lys-Pro-Arg-Lys (Compound 10), Arg-Lys-Val-Ala (Compound 15), Lys-Glu-Pro-Ala-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 25), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-A la-Arg-Lys-Val-Ala-Ala-Gln (compound 26), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Ala-Ala-Ala-Gln (compound 29), Lys-Glu-Gly-Val-Pro-Gln-Ala-Lys-P ro-Arg-Lys-Val-Ala-Ala-Gln (compound 31), Lys-Glu-Pro-Val-Gly-Gln-Ala-Lys-G ly-Arg-Lys-Val-Ala-Ala-Gln (compound 34), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys (Compound 38), Glu-Pro-Val-Pro-Gln-Ala-Ala (Compound 48), Asp-Pro-Val-Pro-Gln-Ala-Lys (Compound 49), Asn-Pro-Val-Pro-Gln-Ala-Lys (Compound 50), Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala (Compound 51), Glu-Ala-Val-Pro-Gln-Ala-Lys (Compound 53), Glu-Pro-Val-Pro-Glu-Ala-Lys (Compound 55), Lys-D-Glu-Pro-Val-Pro-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 62), Lys-Glu-Pro-Val-D-Pro-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 65), Lys-Glu-Pro-Val-Pro-D-Gln-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 66), Lys-Glu-Pro-Val-Pro-Gln-D-Ala-Lys- Pro-Arg-Lys-Val-Ala-Ala-Gln (Compound 67), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-D-Arg-Lys-Val-Ala-Ala-Gln (compound 70), Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pr o-Arg-Lys-Val-Ala-Ala-D-Gln (compound 75), Glu-Pro-Val-Pro-Gln-D-Ala-Lys (Compound 83), Lys-Glu-Pro-Val-Pro (Compound 85), Glu-Pro-Val-Pro-Gln (Compound 86), Val-Pro-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala -Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 88), Pro-Ala-Tyr-Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Gln (compound 90), Arg-Lys-Asp-Val-Tyr-Glu-Pro-Val-Pro-Gln-Ala-Lys (compound 93), Ser-Ser-Glu-Asp-Ile-Lys-Glu-Pro-Val-Pro-Gln (compound 99), or Lys-Glu-Pro-Val-Pro-Gln-Ala-Lys-Pro-Arg-Lys-Val-Ala-Ala-Glu (compound 103), 2. A compound according to claim 1 or a physiologically acceptable salt thereof.

19. 20. Use of a compound or a physiologically acceptable salt according to any one of claims 1 to 18 in the manufacture of a medicament for treating enteritis.

20. Enteritis includes specific enteritis and non-specific enteritis, further specific enteritis includes inflammatory bowel disease, necrotizing enteropathy and intestinal dysbiosis, further inflammatory bowel disease includes ulcerative colitis; 20. Use according to claim 19.

21. A pharmaceutical composition comprising a compound or a physiologically acceptable salt thereof according to any one of claims 1 to 18, and a medicamentous excipient.

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