Fragments as Novel Starting Points for tRNA-Guanine Transglycosylase Inhibitors Found by Alternative Screening Strategies.

ABSTRACT: Crystallography provides structural information crucial for fragment optimization, however several criteria must be met to screen directly on protein crystals as soakable, well-diffracting specimen must be available. We screened a 96-fragment library against the tRNA-modifying enzyme TGT using crystallography. Eight hits, some with surprising binding poses, were detected. However, the amount of data collection, reduction and refinement is assumed substantial. Therefore, having a reliable cascade of fast and cost-efficient methods available for pre-screening before embarking to elaborate crystallographic screening appears beneficial. This allows filtering of compounds to the most promising hits, available to rapidly progress from hit-to-lead. But how to ensure that this workflow is reliable

SUBMITTER: Hassaan E 

PROVIDER: S-EPMC7687107 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature