Discovery of an Anion-Dependent Farnesyltransferase Inhibitor from a Phenotypic Screen.

ABSTRACT: By employing a phenotypic screen, a set of compounds, exemplified by 1, were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of 1 as affinity bait identified farnesyl transferase (FTase) as the primary interacting protein in cell lysates. This ligand-FTase binding interaction was confirmed via X-ray crystallography and temperature dependent fluorescence studies, despite 1 lacking structural and binding similarity to known FTase inhibitors. Although multiple lines of evidence established the binding interaction, these ligands exhibited minimal inhibitory activity in a cell-free biochemical FTase inhibition ass

SUBMITTER: Bukhtiyarova M 

PROVIDER: S-EPMC7812668 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature