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Synthesis and hypoglycemic activity studies of novel glucagon-like peptide-1 analogues

ZHOU Feng;CHEN Xinyu;FEI Yingying;HAN Jing;College of Chemistry and Materials Science,Jiangsu Normal University;  
Objective A novel glucagon-like peptide-1(GLP-1)receptor agonist,Xenopuslaevis GLP-1 with a novel peptide sequence was synthesized and modified(XenGLP-1)for controlled release.Methods The current work was initiated with the introduction of the C-terminal tail(PSSGAPPPS)of exendin-4 into XenGLP-1 to achieve improved stability and activity.Cysteine was then introduced to XenGLP-1.Maleimide modified polyethylene glycol 2 000(PEG2 000)was then straight forward attached to the thiol group of cysteine with high chemical selectivity to obtain PEG2 000-ZF-1 and PEG2 000-ZF-2.Results The long-acting hypoglycemic effect of PEG2 000-ZF-1 and PEG2 000-ZF-2 was investigated to identify its efficiency for anti-diabetics.Conclusion The 2 PEG conjugated peptides have long acting hypoglycemic activity and have good prospects for drug development.
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