Advances of N-terminal modifications of GLP-1 and their applications for the treatment of type 2 diabetes

doi:10.5246/jcps.2015.11.090

Abstract

Abstract:

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with excellent blood glucose-lowering activity, however, it is rapidly inactivated in the plasma mainly by dipeptidyl peptidase IV (DPP-IV). To overcome this problem, various N-terminal modifications of GLP-1 have been performed to prolong the in vivo biological activity,by improving the DPP-IV resistance while retaining receptor affinity and receptor activation. These studies have included modifications of His⁷, Ala⁸or Glu⁹ at the N-terminus of GLP-1 and some other modifications. Among them, Ala⁸ substitutions with glycine (Gly⁸) and α-aminoisobutyric acid (Aib⁸) have been clinically applied in the development of diabetic therapy, such as Exenatide, Semaglutide, Albiglutide and Taspoglutide. In this review, we introduce N-terminal modifications of GLP-1 that have been reported, and discuss their potential and challenges for the treatment of type 2 diabetes.

Key words: GLP-1 analogues, DPP-IV, N-terminal modification, Type 2 diabetes

CLC Number:

R914

Supporting:

Xiaohui Bai, Youhong Niu, Decai Xiong, Yanfen Wu, Yunsen Li. Advances of N-terminal modifications of GLP-1 and their applications for the treatment of type 2 diabetes[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(11): 701-711.

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