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含苯丙氨酸的异羟肟酸作为IIb类组蛋白去乙酰化酶（HDAC）的选择性抑制剂。

Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs).

作者信息

Schäfer Stefan, Saunders Laura, Eliseeva Elena, Velena Alfredo, Jung Mira, Schwienhorst Andreas, Strasser Anja, Dickmanns Achim, Ficner Ralf, Schlimme Sonja, Sippl Wolfgang, Verdin Eric, Jung Manfred

机构信息

Institute of Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany.

出版信息

Bioorg Med Chem. 2008 Feb 15;16(4):2011-33. doi: 10.1016/j.bmc.2007.10.092. Epub 2007 Nov 4.

DOI:10.1016/j.bmc.2007.10.092
PMID:18054239
Abstract

We synthesized biarylalanine-containing hydroxamic acids and tested them on immunoprecipitated HDAC1 and HDAC6 and show a subtype selectivity for HDAC6 that was confirmed in cells by Western blot (tubulin vs histones). We obtained an X-ray structure with a HDAC6-selective inhibitor with the bacterial deacetylase HDAH. Docking studies were carried out using HDAC1 and HDAC6 protein models. Antiproliferative activity was shown on cancer cells for selected compounds.

摘要

我们合成了含联芳基丙氨酸的异羟肟酸，并在免疫沉淀的HDAC1和HDAC6上对其进行测试，结果表明对HDAC6具有亚型选择性，这一点通过蛋白质印迹法（微管蛋白与组蛋白）在细胞中得到了证实。我们获得了一种HDAC6选择性抑制剂与细菌脱乙酰酶HDAH的X射线晶体结构。使用HDAC1和HDAC6蛋白质模型进行了对接研究。所选化合物在癌细胞上显示出抗增殖活性。

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