Targeting epigenetic reader domains by chemical biology. (August 2020)

• Record Type: Journal Article
• Authors: Cipriano, Alessandra; Sbardella, Gianluca; Ciulli, Alessio
• Is Part Of: Current opinion in chemical biology. Volume 57(2020)
• Page Start: 82
• Page End: 94
• Publication Date: 2020-08
• Subjects: Bromodomain -- Reader domains -- Post-translational modifications -- Photo-affinity probes -- PROTACs; Bioorganic chemistry -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Clinical biochemistry -- Periodicals; Biochemistry -- Periodicals; Chimie bio-organique -- Périodiques; Biologie -- Périodiques; 572.05
• DOI: 10.1016/j.cbpa.2020.05.006
• Languages: English
• ISSNs: 1367-5931

Abstract

Abstract: Over the past years, growing interest toward post-translational modifications (PTMs) of histones and nonhistone proteins has prompted academia and industrial research groups to develop different approaches to better understand the link between PTMs and pathological states. Selective recognition of PTMs is carried out by reader modules, which mediate the biological readout of epigenetic mechanisms. Progress in medicinal chemistry and chemical biology has contributed to corroborate the role of reader domains in chromatin-binding proteins as potential therapeutic targets. Here, we review the state-of-the-art of the most important small molecules developed to date, with a particular attention on contemporary chemical biology approaches, including photoaffinity probes, cyclic peptides, bifunctional inhibitors, and PROTAC degraders.