Inhibition of bromodomain-mediated proteinprotein interactions as a novel therapeutic strategy

• Main Authors: Furdas, Silviya D, Carlino, Luca, Sippl, Wolfgang, Jung, Manfred
• Format: Journal Article
• Language: English
• Published: 01.02.2012
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c1md00201e

A multitude of epigenetic regulatory mechanisms is reflected in the dynamic nature of chromatin during different development stages as well as pathological states of human organisms. Apart from enzymatic processes, the recognition of histone modifications by reader protein modules contributes to the equilibrium between transcriptionally active and silent chromatin. Bromodomains are involved in the recognition of acetylated lysine containing substrates and in the downstream signalling of histone acetylation. In part, this is mediated by the regulation of further acetylation reactions. Development of small molecules as epigenetic tools able to block proteinprotein interactions provided by bromodomains is a new emerging focus of epigenetic research, which also holds great potential for novel therapeutical approaches. This review is dealing with fundamentals of bromodomain structural biology, their inhibitors, and the relevance of these phenomena to molecular biology and drug discovery. Small molecule inhibitors of acetyl lysinebromodomain interactions emerge as novel epigenetic tools with potential for therapeutic approaches.