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Fluorescence Polarization for the Evaluation of Small‐Molecule Inhibitors of PCAF BRD/Tat‐AcK50 Association
Author(s) -
Hu Ping,
Wang Xinghui,
Zhang Baiqun,
Zhang Shuai,
Wang Qiang,
Wang Zhiyong
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300499
Subject(s) - pcaf , chemistry , bromodomain , fluorescence , small molecule , pyridine , molecule , combinatorial chemistry , cancer research , biochemistry , acetylation , medicinal chemistry , organic chemistry , medicine , physics , quantum mechanics , gene
A fluorescence polarization competitive assay was developed to efficiently screen and evaluate inhibitors of PCAF bromodomain/Tat‐AcK50 protein–peptide interaction. A series of pyridine 1‐oxide derivatives were synthesized and evaluated. Some of the novel compounds, 2‐(3‐aminopropylamino) pyridine 1‐oxide derivatives, could be effective inhibitors of PCAF bromodomain/Tat‐AcK50 association. Specifically, 2‐(3‐aminopropylamino)‐5‐(hydroxymethyl)pyridine 1‐oxide hydrochloride ( 15 ) and the 5‐((3‐aminopropylamino)methyl) derivative ( 20 ) were found to be effective ligands for the PCAF BRD pocket. First preliminary cellular studies indicate that these small‐molecule inhibitors have lower cytotoxicities and are potential leads for the anti‐HIV/AIDS therapeutic strategy by targeting host‐cell protein PCAF BRD to block HIV replication.

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