Structure-based design of conformationally constrained cyclic peptidomimetics to target the MLL1-WDR5 protein–protein interaction as inhibitors of the MLL1 methyltransferase activity

作     者：Hacer Karatas Shirley Y.Lee Elizabeth C.Townsend Fang Cao Jing Xu Denzil Bernard Liu Liu Yali Dou Shaomeng Wang 

作者机构：Department of Medicinal ChemistryUniversity of Michigan Department of Internal MedicineUniversity of Michigan Department of PathologyUniversity of Michigan Comprehensive Cancer CenterUniversity of Michigan Department of PharmacologyUniversity of Michigan 

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

年 卷 期：2015年第26卷第4期

页      面：455-458页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：supported by grants from the National Institutes of Health USA (No.CA177307 to SW and YD) 

主　　题：EpigeneticsMLL1 histone methyltransferaseWDRS MLLI interactionSmall molecule inhibitorsCyclic peptidomemtics 

摘      要：We described herein structure-based design, synthesis and evaluation of conformationally constrained, cyclic peptidomimetics to block the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 histone methyltransferase activity. Our study has yielded cyclic peptidomimetics with very high binding affinities to WDR5 （Ki values 〈1 nmol/L） and function as antagonists of the MLL1 histone methyltransferase activity.