The invention discloses a novel BimBH3 mimic
peptide analogue constructed on the basis of a nailing and
fatty acid acylation dual-modification strategy and application of the novel BimBH3 mimic
peptide analogue serving as a PTPN1 inhibitor to development of a long-acting hypoglycemic
drug. The structural general formula of the BimBH3 mimic
peptide analogue is as shown in a formula I. The structural general formula of the BimBH3 mimic peptide analogue is as shown in a formula I. The invention provides the BimBH3 mimic peptide analogue with a novel structure, and the BimBH3 mimic peptide analogue is constructed by adopting a nailing and
fatty acid acylation dual-modification strategy and has the structural general formula as shown in the formula I. The invention further provides a preparation method of the BimBH3 mimic peptide analogue. On the basis of a BimBH3 functional domain core sequence, the novel BimBH3 mimic peptide analogue has target inhibitory activity,
metabolic stability and in-vivo action durability through second-site
lysine substitution, N-terminal
palmitic acid conjugation and fifth, sixth and ninth site
glutamic acid side chain mediated synthesis ring nailing modification, and the synthesis ring nailing mode is molecular
lactam cyclization. Experiments show that the compound can efficiently inhibit PTPN1 activity, has a long-acting hypoglycemic effect in a type 2 diabetes
animal model, and has the potential of being developed into a long-acting antidiabetic
drug which is administered once a week. The invention also discloses a
solid-
phase synthesis preparation method of the compound and application of the compound as a potential PTPN1 inhibitor
drug.