New Potent Bisubstrate Inhibitors of Histone Acetyltransferase p300: Design, Synthesis and Biological Evaluation

被引：15
|
作者：
Kwie, Franciane Ho A. [1 ,2 ]
Briet, Martine [2 ,3 ]
Soupaya, David [1 ,2 ]
Hoffmann, Pascal [1 ,2 ]
Maturano, Marie [1 ,2 ]
Rodriguez, Frederic [1 ,2 ]
Blonski, Casimir [1 ,2 ]
Lherbet, Christian [1 ,2 ]
Baudoin-Dehoux, Cecile [1 ,2 ]
机构：
[1] CNRS, UMR 5068, SPCMIB, Lab Synth & Phys Chim Mol Interet Biol, F-31062 Toulouse 9, France
[2] Univ Toulouse, SPCMIB, UPS, Lab Synth & Phys Chim Mol Interet Biol, F-31062 Toulouse 9, France
[3] CNRS, UMR 508, LBCMCP, F-31062 Toulouse 9, France
来源：
CHEMICAL BIOLOGY & DRUG DESIGN | 2011年 / 77卷 / 01期
关键词：
bisubstrate inhibitor; chemical biology; drug design; HAT; p300; SMALL-MOLECULE; CHROMATIN TRANSCRIPTION; SCORING FUNCTIONS; COENZYME-A; PROTEIN; DOCKING; HATS; IDENTIFICATION; ACETYLATION; EPIGENETICS;
D O I：
10.1111/j.1747-0285.2010.01056.x
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Bisubstrate-type compound Lys-CoA has been shown to inhibit the p300 histone acetyl transferase activity efficiently and may constitute a lead compound for a novel class of anticancer therapeutics. Based on this strategy, we synthesized a series of CoA derivatives and evaluated these molecules for their activity as p300 histone acetyltransferases inhibitor. The best activity was obtained with compound 3 bearing a C-5 spacing linker that connects the CoA moiety to a tert-butyloxycarbonyl (Boc) group. Based on docking simulations, this inhibitor exhibits favorable interactions with two binding areas, namely pockets P1 and P2, within the active site.
引用
收藏
页码：86 / 92
页数：7
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