Process of Fragment-Based Lead Discovery-A Perspective from NMR.

ABSTRACT: Fragment-based lead discovery (FBLD) has proven fruitful during the past two decades for a variety of targets, even challenging protein-protein interaction (PPI) systems. Nuclear magnetic resonance (NMR) spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power to probe the intrinsically weak interactions between targets and low-molecular-weight fragments. Here, we review the NMR FBLD process from initial library construction to lead generation. We describe technical aspects regarding fragment library design, ligand- and protein-observed screening, and protein-ligand structure model generation. For weak binders, the initial hit-to-lead evolution can be guided by structural information retrieved from NMR spectroscopy, including chemical

SUBMITTER: Ma R 

PROVIDER: S-EPMC6273320 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature