Design, synthesis and biological evaluation of novel peptide MC62 analogues as potential antihyperglycemic agents

•Two series of MC62 analogues were synthesized.•Both were evaluated for their antihyperglycemic effects.•The antihyperglycemic effect of II-3 was more potent than parent peptide MC62.•This underwent further screening for antihyperglycemic and antioxidative effects.

Two series of peptide MC62 analogues were synthesized, characterized and evaluated for their antihyperglycemic effects. Structure–activity relationship studies of the first series indicated that antihyperglycemic effects were correlated to residues 4, 5, 7 and 8. Peptide I-6 exhibited higher antihyperglycemic activity than the MC62 parent peptide, and was chosen for further modification. Incorporation of Met at position 3 increased potency further and generated II-3, which was screened in vivo and in vitro using exenatide (Ex-4) and GLP-1 as positive controls. The results showed that the antihyperglycemic and antioxidative activities of II-3 were comparable to the positive controls, suggesting II-3 could be a candidate for use as a future diabetic treatment.

Graphical abstractStructure–activity relationships of peptide MC62 resulted in development of compound II-3 that exhibited more potent antihyperglycemic and antioxidative effects in vivo and in vitro.Figure optionsDownload full-size imageDownload as PowerPoint slide