Synthesis and Bioactivity Evaluation of Dipeptidyl Peptidase IV Resistant Glucagon-like Peptide-1 Analogues

Title: Synthesis and Bioactivity Evaluation of Dipeptidyl Peptidase IV Resistant Glucagon-like Peptide-1 Analogues

Volume: 17 Issue: 10

Author(s): Jinpei Zhou, Shuaijian Ni, Huibin Zhang, Hai Qian, Yushi Chi, Wenlong Huang, Lu Yu, Xiaowen Hu and Wei Chen

Affiliation:

Keywords: Glucagon-like peptide-1, microwave assisted synthesis, solid phase peptide synthesis, hypoglycemic

Abstract: Glucagon-like peptide -1 (GLP-1) is an incretin hormone displaying glucose-dependent stimulation of insulin secretion and trophic effects on the pancreatic β-cells. However, GLP-1 is rapidly degraded to GLP-1(9-36) by dipeptidyl peptidase-IV (DPP-IV), which removes the N-terminal dipeptide His7-Ala8. The rapid inactivation of GLP-1 in the blood circulation limits its clinical application. Hence, we replaced the enzymatic hydrolyzation position Ala8 with other natural amino acids. The GLP-1 analogues were synthesized rapidly and efficiently under microwave irradiation, using Fmoc/tBu orthogonal protection strategy. Studies on blood-glucose-lowering effect of GLP-1 analogues in vivo were undertaken using 10-week-old male Kunming mice. The metabolic stability was tested by incubation with dipeptidyl peptidase-IV (DPP-IV). Generally, Xaa8-GLP-1 analogues exhibit resistance to DPP-IV degradation in vitro and stronger hypoglycemic effect than GLP-1. This may help to understand the structure-activity relationship of GLP-1 analogues.

Cite this article as:

Zhou Jinpei, Ni Shuaijian, Zhang Huibin, Qian Hai, Chi Yushi, Huang Wenlong, Yu Lu, Hu Xiaowen and Chen Wei, Synthesis and Bioactivity Evaluation of Dipeptidyl Peptidase IV Resistant Glucagon-like Peptide-1 Analogues, Protein & Peptide Letters 2010; 17 (10) . https://dx.doi.org/10.2174/092986610792231546