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Design, Synthesis, and Biological Evaluation of Novel Peptide Gly 3 ‐ MC 62 Analogues as Potential Antidiabetic Agents
Author(s) -
Yang Baowei,
Zhang Chenyu,
Li Xue,
Yan Sijia,
Wei Wei,
Wang Xuekun,
Deng Xin,
Huang Wenlong,
Qian Hai
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12564
Subject(s) - chemistry , islet , peptide , lysine , diabetes mellitus , stereochemistry , insulin , pancreatic islets , amino acid , biochemistry , pharmacology , medicine , endocrinology
Two series of conformationally constrained analogues from Gly 3 ‐ MC 62 were designed by scanning the residues Lys 1 , Thr 2 , Met 4 , Lys 5 , Met 7, and Ala 8 with an i‐(i + 2) lactam bridge consisting of a Glutamic acid–xaa–lysine (Glu–Xaa–Lys) scaffold and a diproline fragment. They were synthesized and evaluated for their antihyperglycemic effects. Through screening in normal and mice with diabetes mellitus, peptides II ‐5 , III ‐3 , III ‐4 , and III ‐5 showed significant improvement in antihyperglycemic and antioxidative activities compared with Gly 3 ‐ MC 62 , especially the compound III ‐4 . The primary mechanism of the compounds ( II ‐5 , III ‐3 , III ‐4 , and III ‐5 ) underlying this effect is the islet β ‐cells against oxidative damage induced by STZ , and III ‐4 ‐treated mice showed considerable improvement in the preservation of beta cells in the pancreatic islets of DM mice. These data suggested that III ‐4 could be candidate for the future treatment of diabetes mellitus.