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Synthesis and Biochemical Evaluation of Biotinylated Conjugates of Largazole Analogues: Selective Class I Histone Deacetylase Inhibitors
Author(s) -
Zhao Le,
Dunne Christine E.,
Clausen Dane J.,
Roberts Justin M.,
Paulk Joshiawa,
Liu Haining,
Wiest Olaf G.,
Bradner James E.,
Williams Robert M.
Publication year - 2017
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.201600130
Subject(s) - chemistry , biotinylation , conjugate , moiety , histone deacetylase , thiazole , biotin , histone deacetylase inhibitor , biochemistry , combinatorial chemistry , stereochemistry , histone , gene , mathematical analysis , mathematics
The synthesis of biotinylated conjugates of synthetic analogues of the potent and selective histone deacetylase (HDAC) inhibitor largazole is reported. The thiazole moiety of the parent compound's cap group was derivatized to allow the chemical conjugation to biotin. The derivatized largazole analogues were assayed across a panel of HDACs 1–9 and retained potent and selective inhibitory activity towards the class I HDAC isoforms. The biotinylated conjugate was further shown to pull down HDACs 1, 2, and 3.