摘要
目的寻找高效、长效的新型GLP-1受体激动剂。方法非洲爪蟾GLP-1(XenGLP-1)的半衰期较短,设计三个半胱氨酸改构的XenGLP-1类似物,优选高降糖活性的多肽进一步PEG化修饰。结果 PEG-XenGLP-1缀合肽具有优异的长效降糖活性。结论从动物源寻找新型GLP-1类药物是降糖药物研究的新思路。对GLP-1类多肽进行PEG化修饰,可在降糖活性保持的前提下显著延长多肽的半衰期。
OBJECTIVE To search novel GLP-1 receptor agonists based on animal GLP-1 sequence,and represents a facile and useful method for developing novel GLP-1 analogs.METHODS The biological activities of XenGLP-1 is limited by its short half-lives.In this study,Cysteine was first introduced to XenGLP-1 and three XenGLP-1 analogs were synthesized,and the selected peptides were further PEGlyated to improve the half-life.RESULTS The glucose-lowering and long-term hypoglycemic activities of PEGlyated XenGLP-1 conjugates were improved.CONCLUSION Searching novel GLP-1 receptor agonists based on animal GLP-1 sequence represents a facile and useful method for developing novel GLP-1 analogs.Peptide chemical conjugated with PEG would not influence the hypoglycemic activity and could improve the long-term glucose-lowering activity.
出处
《海峡药学》
2017年第12期51-55,共5页
Strait Pharmaceutical Journal
基金
国家自然科学基金青年项目(81602964)
江苏高校品牌专业建设工程项目(专业序号PPZY2015B110)
