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

Eur J Med Chem. 2014 Feb 12:73:105-11. doi: 10.1016/j.ejmech.2013.11.043. Epub 2013 Dec 12.

Abstract

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.

Keywords: Antihyperglycemic; Antioxidative; Diabetes mellitus; MC62 peptide; Streptozotocin; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antioxidants / metabolism
  • Blood Glucose / analysis
  • Cell Line, Tumor
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Drug Design*
  • Glucose Tolerance Test
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Oxidative Stress / drug effects
  • Pancreas / drug effects
  • Pancreas / pathology
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / therapeutic use
  • Protein Conformation
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Blood Glucose
  • Hypoglycemic Agents
  • Peptides