Synthesis and Biochemical Evaluation of Biotinylated Conjugates of Largazole Analogues: Selective Class I Histone Deacetylase Inhibitors

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 a...

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Published inIsrael journal of chemistry Vol. 57; no. 3-4; pp. 319 - 330
Main Authors Zhao, Le, Dunne, Christine E., Clausen, Dane J., Roberts, Justin M., Paulk, Joshiawa, Liu, Haining, Wiest, Olaf G., Bradner, James E., Williams, Robert M.
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 01.04.2017
Subjects
Biochemistry
biotin
cancer
Chromatin
Conjugates
Conjugation
Histones
Inhibitors
largazole
Panels
Parents
peptidomimetics
Synthesis
inhibitors
cancer
peptidomimetics
biotin
largazole
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Summary: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.
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ISSN:0021-2148
1869-5868
DOI:10.1002/ijch.201600130