拉加唑类似物生物素化缀合物的合成与生化评价：选择性I类组蛋白去乙酰化酶抑制剂
Synthesis and Biochemical Evaluation of Biotinylated Conjugates of Largazole Analogues: Selective Class I Histone Deacetylase Inhibitors.
作者信息
Zhao Le, Dunne Christine E, Clausen Dane J, Roberts Justin M, Paulk Joshiawa, Liu Haining, Wiest Olaf G, Bradner James E, Williams Robert M
机构信息
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523 (USA).
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 (USA).
出版信息
Isr J Chem. 2017 Apr;57(3-4):319-330. doi: 10.1002/ijch.201600130. Epub 2017 Jan 27.
Abstract
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.
摘要
据报道，已合成强效选择性组蛋白去乙酰化酶（HDAC）抑制剂拉加唑的合成类似物的生物素化缀合物。母体化合物帽基团的噻唑部分经衍生化以实现与生物素的化学缀合。对一系列HDAC 1 - 9对衍生化的拉加唑类似物进行了测定，这些类似物对I类HDAC亚型保留了强效和选择性抑制活性。进一步表明，生物素化缀合物能够下拉HDAC 1、2和3。
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