Patent ID: 11970523
Assignee: CHINA PHARMACEUTICAL UNIVERSITY
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 0:
1. A compound having a general formula His-Xaa1-PP1-Xaa2-PP2-Xaa3 and its pharmaceutically acceptable salt, wherein
PP1 is a polypeptide selecting from the group of polypeptides having the amino acid sequences shown as SEQ ID NO.:02, SEQ ID NO.:04 and SEQ ID NO.:05; PP2 is a polypeptide selecting from the group of polypeptides having the amino acid sequences shown as SEQ ID NO.:03, SEQ ID NO.:06, SEQ ID NO.:07 and SEQ ID NO.:08; PP1 is the polypeptide selecting from the group of polypeptides having the amino acid sequences shown as SEQ ID NO.:02, SEQ ID NO.:04 and SEQ ID NO.:05 when PP2 is the polypeptide having the amino acid sequence shown as SEQ ID NO.:03; PP1 is the polypeptide having the amino acid sequence shown as SEQ ID NO.:05 when PP2 is the polypeptide selecting from the group of polypeptides having the amino acid sequences shown as SEQ ID NO.:06, SEQ ID NO.:07 and SEQ ID NO.:08;
wherein
Xaa1 is selected from the group consisting of Gly, Aib, D-Ser, Ser, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Pro, Thr, Trp, Tyr and Val;
Xaa2 is selected from the group consisting of Cys,, wherein X is —CH3 or —COOH;
Y is —NH—CO— or —CO—NH—;
n is a natural number selected from 0 to 20;
m is a natural number selected from 1 to 20; and
Xaa3 is Ser-OH or Ser-NH2;

wherein the compound is prepared by the following step:
step 1: taking and activating resin, and then gradually coupling amino acids, so as to obtain first peptide resin;
step 2: taking the first peptide resin, and coupling a fatty acid chain small molecule of Formula I or Formula II to a Lys side chain to obtain second peptide resin; and
step 3: taking the second peptide resin, and performing lysis and purification to obtain the compound having the general formula His-Xaa1-PP1-Xaa2-PP2-Xaa3;, wherein R1 is selected from tBu, Dmab, or Bzl;
R2 is selected from methyl, ethyl, tert-butyl, and benzhydryl; and
a Lys side chain protecting group coupled to the fatty acid chain small molecule of Formula I or Formula II is selected from Fmoc, Boc, Dde, or ivDde;
wherein the purity of the compound is higher than 85%; the compound maintains hypoglycemic activity for more than 40 hours.