New Potent Bisubstrate Inhibitors of Histone Acetyltransferase p300: Design, Synthesis and Biological Evaluation
| Autor: | Cécile Baudoin-Dehoux, Casimir Blonski, Frédéric Rodriguez, David Soupaya, Pascal Hoffmann, Martine Briet, Franciane Ho A Kwie, Marie Maturano, Christian Lherbet |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Pharmacology
Histone Acetyltransferases Histone Acetyltransferase p300 biology Chemistry Stereochemistry Organic Chemistry Active site Biochemistry Combinatorial chemistry chemistry.chemical_compound Histone Docking (molecular) Drug Discovery biology.protein Molecular Medicine Transferase Linker Lead compound |
| Zdroj: | Chemical Biology & Drug Design. 77:86-92 |
| ISSN: | 1747-0277 |
| DOI: | 10.1111/j.1747-0285.2010.01056.x |
| 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: |
|
Plný text