Back to Search
Start Over
New potent bisubstrate inhibitors of histone acetyltransferase p300: design, synthesis and biological evaluation.
- Source :
-
Chemical biology & drug design [Chem Biol Drug Des] 2011 Jan; Vol. 77 (1), pp. 86-92. Date of Electronic Publication: 2010 Nov 30. - Publication Year :
- 2011
-
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.<br /> (© 2010 John Wiley & Sons A/S.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1747-0285
- Volume :
- 77
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Chemical biology & drug design
- Publication Type :
- Report
- Accession number :
- 21118378
- Full Text :
- https://doi.org/10.1111/j.1747-0285.2010.01056.x