Exendin-4类似物的生物活性及结构  

Bioactivity and Structure of Analogues of Exendin-4

作　　者：宋相伟[1] 王雪丽[2] 熊新辉[1] 牛建丽[1] 王仕擎[3] 王丽萍[1] 李惟[1] 

机构地区：[1]吉林大学生命科学学院生物大分子实验室,长春130021 [2]吉林大学生命科学学院分子酶学工程教育部重点实验室,长春130021 [3]吉林大学生物与农业工程学院,长春130022

出　　处：《高等学校化学学报》2008年第6期1163-1165,共3页Chemical Journal of Chinese Universities

基　　金：长春市振兴老工业基地科技公关及市、院合作计划课题(批准号:04-02GG221)资助

摘　　要：Exendin-4 is an incretin mimetic that has been studied as a potent drug for the treatment of the type 2 diabetes. To screen the shorter analogues of Exendin-4 that have the same bioactivity,we designed two analogues of Exendin-4: Ex1,deleting this sequence and Ex2,replacing this sequence with three Alas. The proliferation assay of RINm-5F cell using MTT suggested the bioactivity of Ex1 and Ex2 was lower compared to that of Exendin-4 caused by the deletion of LSKQMEEEA. Ex1 and Ex2 had the same strong stability against DPPⅣ with Exendin-4. CD data suggested the helix content of Ex1 had a significant lost,but the helix content of Ex2 was the same as that of Exendin-4. The emission maximum of Ex1 was red-shifted of 3 nm relative to Exendin-4,the absence of this sequence made Trp25 more apt to hydrophilic and the Trp-cage became looser. So we have designed Ex2,the mimetic of Exendin-4 that had the same bioactivity and strong stability against DPPⅣ with Exendin-4 successfully. It became a solid foundation for designing shorter analogues of Exendin-4 for oral drug of diabetes.Exendin-4 is an incretin mimetic that has been studied as a potent drug for the treatment of the type 2 diabetes. To screen the shorter analogues of Exendin-4 that have the same bioactivity, we designed two analogues of Exendin-4 ： Ex1, deleting this sequence and Ex2, replacing this sequence with three Alas. The proliferation assay of RINm-5F cell using MTT suggested the bioactivity of Ex1 and Ex2 was lower compared to that of Exendin-4 caused by the deletion of LSKQMEEEA. Ex1 and Ex2 had the same strong stability against DPPⅣ with Exendin-4. CD data suggested the helix content of Ex1 had a significant lost, but the helix content of Ex2 was the same as that of Exendin-4. The emission maximum of Ex1 was red-shifted of 3 nm relative to Exendin-4, the absence of this sequence made Trp25 more apt to hydrophilic and the Trp-cage became looser. So we have designed Ex2, the mimetic of Exendin-4 that had the same bioactivity and strong stability against DPPⅣ with Exendin-4 successfully. It became a solid foundation for designing shorter analogues of Exendin-4 for oral drug of diabetes.

关 键 词：Exendin-4类似物 螺旋结构 稳定性 生物活性 

分 类 号：O629[理学—有机化学]