Discovery of drug-like inhibitors of an essential RNA-editing ligase in Trypanosoma brucei.

ABSTRACT: Trypanosomatid RNA editing is a unique process and essential for these organisms. It therefore represents a drug target for a group of protozoa that includes the causative agents for African sleeping sickness and other devastating tropical and subtropical diseases. Here, we present drug-like inhibitors of a key enzyme in the editing machinery, RNA-editing ligase 1 (REL1). These inhibitors were identified through a strategy employing molecular dynamics to account for protein flexibility. A virtual screen of the REL1 crystal structure against the National Cancer Institute Diversity Set was performed by using AutoDock4. The top 30 compounds, predicted to interact with REL1's ATP-binding pocket, were further refined by using the relaxed complex scheme (RCS), which redocks the compounds to rece

SUBMITTER: Amaro RE 

PROVIDER: S-EPMC2577703 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature