Optimization of the interligand Overhauser effect for fragment linking: application to inhibitor discovery against Mycobacterium tuberculosis pantothenate synthetase.

ABSTRACT: Fragment-based methods are a new and emerging approach for the discovery of protein binders that are potential new therapeutic agents. Several ways of utilizing structural information to guide the inhibitor assembly have been explored to date. One of the approaches, application of interligand Overhauser effect (ILOE) observations, is of particular interest, as it does not require the availability of a three-dimensional protein structure and is an NMR-based method that can be applied to targets that cannot be observed directly because of their size. Fragments, as small and often hydrophobic molecules, suffer from problems including compound aggregation in an aqueous environment and nonspecific binding contributions, especially when screened at higher concentrations suitable for ILOE observa

SUBMITTER: Sledz P 

PROVIDER: S-EPMC4441724 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature