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Selective n-terminal modification of peptides and proteins:Recent progresses and applications

Chinese Chemical Letters 2022年第1期33卷 80-88页

作者： Hongfei Jiang Wujun Chen Jie Wang Renshuai Zhang The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute Qingdao 266071China

numerous strategies for linking desired chemical probes with target peptides and proteins have been developed and applied in the field of biological *** for site-specific modification of native amino acid residues in test tubes and biological contexts represent novel biological tools for understanding the role of peptides and *** n-terminal modification strategies have been broadly studied especially in the last 10 years,as n-terminal positions are typically solvent exposed and provide chemically distinct sites for many peptide and protein targets,making n terminus distinct from other functional groups.A growing number of chemical and enzymatic techniques have been developed to modify n-terminal amino acids,and those techniques have the potential in the fields of medicine,basic research and applied materials *** review focuses on appraising modification methodologies with the potential for biological applications from the past 10 years.

关键词： n-terminal modification n-terminal ligation Terminus modification Peptide modification Protein modification

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

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Journal of Chinese Pharmaceutical Sciences 2015年第11期24卷 701-711页

作者：白晓辉牛有红熊德彩吴艳芬李云森北京大学医学部天然药物及仿生药物国家重点实验室北京100191 苏州沪云肿瘤研究中心有限公司江苏苏州215123

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, Ala8 or 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.

关键词： GLP-1 analogues DPP-IV n-terminal modification Type 2 diabetes

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