Potent Inhibition of Nicotinamide <i>N</i>-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
Yongzhi Gao, Matthijs J. van Haren, Ned Buijs, Paolo Innocenti, Yurui Zhang, Davide Sartini, Roberto Campagna, Monica Emanuelli, Richard B. Parsons, Willem Jespers, Hugo Gutiérrez‐de‐Terán, Gerard J. P. van Westen, Nathaniel I. Martin
Abstract
value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.
Topics & Concepts
ChemistryNicotinamideCofactorMoietyMethyltransferaseLinkerStereochemistryEnzymeBiochemistryAlkeneNAD+ kinaseMethylationDNACatalysisComputer scienceOperating systemCRISPR and Genetic EngineeringBiochemical and Molecular ResearchAutophagy in Disease and Therapy