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.
