1. New potent bisubstrate inhibitors of histone acetyltransferase p300: design, synthesis and biological evaluation.
- Author
-
Kwie FH, Briet M, Soupaya D, Hoffmann P, Maturano M, Rodriguez F, Blonski C, Lherbet C, and Baudoin-Dehoux C
- Subjects
- Models, Molecular, Molecular Dynamics Simulation, Protein Binding, Reproducibility of Results, Research Design, Amides chemical synthesis, Amides pharmacology, Coenzyme A chemical synthesis, Coenzyme A pharmacology, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Histone Acetyltransferases antagonists & inhibitors, Histone Acetyltransferases metabolism
- Abstract
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., (© 2010 John Wiley & Sons A/S.)
- Published
- 2011
- Full Text
- View/download PDF