In silico design of anti-tumor mini-protein targeting MDM2

作     者：Jinghui Zhang Huixin Xu Baishi Wang Xuekai Zhang Lei Fu Yannan Li Guanzhao Wu Zitong Zhao Lu Liu Ting Yang Zheyu Zhang Jinbo Yang Tao Jiang Peiju Qiu Rilei Yu Jinghui Zhang;Huixin Xu;Baishi Wang;Xuekai Zhang;Lei Fu;Yannan Li;Guanzhao Wu;Zitong Zhao;Lu Liu;Ting Yang;Zheyu Zhang;Jinbo Yang;Tao Jiang;Peiju Qiu;Rilei Yu

作者机构：Key Laboratory of Marine DrugsChinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China Innovation Center for Marine Drug Screening&Evaluation Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266003China Department of Biological EngineeringCollege of Chemical and Biological EngineeringShandong University of Science and TechnologyQingdao 266590China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2023年第34卷第5期

页      面：256-258页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 0703[理学-化学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.3217110331 and 8212200560) Major new drug development in Shandong Province(No.2020CXGC010503) 

主　　题：Protein design Antitumor agents In silico design Constrained peptide Epitope grafting 

摘      要：We designed a disulfide-crosslinked mini-protein with a two-helical topology consisting of L-and Damino acids,which was exceptionally stable in ***,we further used it as a scaffold to design mini-proteins targeting p53 positive tumor *** on bifunctional grafting,key residues from the transactivation domain of p53 and a designed unnatural amino acid were grafted into the helix constituted by L-amino acids to confer the mini-protein with MDM2 inhibitory ***,ten Arg residues were introduced to improve its membrane penetrating *** the mini-proteins,UPROL-10e showed nano-molar binding affinity on MDM2 and cellular toxicity on p53 expressing HCT116cells.