New potent bisubstrate inhibitors of histone acetyltransferase p300: design, synthesis and biological evaluation

Autor:	Franciane Ho A, Kwie, Martine, Briet, David, Soupaya, Pascal, Hoffmann, Marie, Maturano, Frédéric, Rodriguez, Casimir, Blonski, Christian, Lherbet, Cécile, Baudoin-Dehoux
Rok vydání:	2010
Předmět:	Models Molecular Research Design Reproducibility of Results Coenzyme A Enzyme Inhibitors Molecular Dynamics Simulation Amides Histone Acetyltransferases Protein Binding
Zdroj:	Chemical biologydrug design. 77(1)
ISSN:	1747-0285
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::0758ccf334a408d7f80ba9cd4d30f043 https://pubmed.ncbi.nlm.nih.gov/21118378 Zobrazit plný text záznamu Plný text