A ligand-observed mass spectrometry approach integrated into the fragment based lead discovery pipeline.

ABSTRACT: In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak bi

SUBMITTER: Chen X 

PROVIDER: S-EPMC4322365 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature