Chemical Epigenetics: The Impact of Chemical and Chemical Biology Techniques on Bromodomain Target Validation

被引：27
作者：
Schiedel, Matthias [1 ]
Moroglu, Mustafa [1 ]
Ascough, David M. H. [1 ]
Chamberlain, Anna E. R. [1 ]
Kamps, Jos J. A. G. [1 ]
Sekirnik, Angelina R. [1 ]
Conway, Stuart J. [1 ]
机构：
[1] Univ Oxford, Dept Chem, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2019年 / 58卷 / 50期
基金：
英国工程与自然科学研究理事会;
关键词：
bromodomains; epigenetics; inhibitors; PROTACs; protein-protein interactions; SMALL-MOLECULE INHIBITORS; CHROMATIN-REMODELING COMPLEX; FRAGMENT-BASED DISCOVERY; STRUCTURE-BASED DESIGN; ACETYLATED HISTONE H4; OBSERVED FLUORINE NMR; E3 UBIQUITIN LIGASE; F-19; NMR; STRUCTURAL BASIS; PROTEIN-STRUCTURE;
D O I：
10.1002/anie.201812164
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Epigenetics is currently the focus of intense research interest across a broad range of disciplines due to its importance in a multitude of biological processes and disease states. Epigenetic functions result partly from modification of the nucleobases in DNA and RNA, and/or post-translational modifications of histone proteins. These modifications are dynamic, with cellular machinery identified to modulate and interpret the marks. Our focus is on bromodomains, which bind to acetylated lysine residues. Progress in the study of bromodomains, and the development of bromodomain ligands, has been rapid. These advances have been underpinned by many disciplines, but chemistry and chemical biology have undoubtedly played a significant role. Herein, we review the key chemistry and chemical biology approaches that have furthered our study of bromodomains, enabled the development of bromodomain ligands, and played a critical role in the validation of bromodomains as therapeutic targets.
引用
收藏
页码：17930 / 17952
页数：23
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