Objective A novel glucagon-like peptide-1(GLP-1) receptor agonist ,Xenopuslaevis GLP-1with 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 intro-duced to XenGLP-1 .Maleimide modified polyethylene glycol 2000 (PEG2000 ) was then straight forward attached to the thiol group of cysteine with high chemical selectivity to obtain PEG 2000-ZF-1 and PEG2000-ZF-2 .Results The long-acting hypoglycemic effect of PEG2000-ZF-1 and PEG2000-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 .%目的 合成具有全新肽序的新型胰高血糖素样肽-1(GLP-1)受体激动剂非洲爪蟾GLP-1并对其(XenGLP-1)进行长效化修饰.方法 先通过在其C端引入PSSGAPPPS序列以增加其降糖活性,再在XenGLP-1序列上引入半胱氨酸,进一步利用MAL-PEG2000与其进行缀合.结果 合成得到PEG2000-ZF-1和PEG2000-ZF-22个缀合肽,并对缀合肽进行长效化降糖活性研究.结论 2个PEG化缀合肽具有长效的降糖活性,具有很好的药物开发前景.
展开▼
