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 methylt...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.展开更多
基金supported by grants from the National Institutes of Health,USA (No.CA177307 to SW and YD)
文摘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.
