Facile synthesis of insulin fusion derivatives through sortase A ligation

作     者：Maria M.Disotuar Jake A.Smith Jinze Li Steve Alam Nai-Pin Lin Danny Hung-Chieh Chou Maria M.Disotuar;Jake A.Smith;Jinze Li;Steve Alam;Nai-Pin Lin;Danny Hung-Chieh Chou

作者机构：Department of BiochemistrySchool of MedicineUniversity of UtahSalt Lake CityUT 84112USA Division of Endocrinology and DiabetesDepartment of PediatricsSchool of MedicineStanford UniversityPalo AltoCA 94305USA 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第9期

页      面：2719-2725页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：supported by NIGMS(GM125001,USA) NIDDK(DK121336,USA) 

主　　题：Diabetes mellitus Insulin synthesis Sortase A(SrtA)ligation Albumin-binding peptide SA21 Long-acting insulin 

摘      要：Insulin derivatives such as insulin detemir and insulin degludec are *** and Drug Administration(FDA)-approved long-acting insulin currently used by millions of people with *** derivatives are modified in C-terminal B29 lysine to retain insulin *** and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic ***,we report a new method using sortase A(SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B *** new insulin molecule(Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin *** further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and in vivo *** enzymatic method can therefore be used for future insulin design and development.