短链羧酸及其异羟肟酸类似物抑制组蛋白脱乙酰酶对脊椎动物发育和神经元染色质的影响
Effect of Inhibiting Histone Deacetylase with Short-Chain Carboxylic Acids and Their Hydroxamic Acid Analogs on Vertebrate Development and Neuronal Chromatin.
作者信息
Fass Daniel M, Shah Rishita, Ghosh Balaram, Hennig Krista, Norton Stephanie, Zhao Wen-Ning, Reis Surya A, Klein Peter S, Mazitschek Ralph, Maglathlin Rebecca L, Lewis Timothy A, Haggarty Stephen J
机构信息
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
出版信息
ACS Med Chem Lett. 2010 Oct 8;2(1):39-42. doi: 10.1021/ml1001954.
Abstract
Carboxylic acids with known central nervous system and histone deacetylase (HDAC) inhibitory activities were converted to hydroxamic acids and tested using a suite of in vitro biochemical assays with recombinant HDAC isoforms, cell based assays in human cervical carcinoma Hela cells and primary cultures from mouse forebrain, and a whole animal (Xenopus laevis) developmental assay. Relative to the parent carboxylic acids, two of these analogs exhibited enhanced potency, and one analog showed altered HDAC isoform selectivity and in vivo activity in the Xenopus assay. We discuss potential uses of these novel hydroxamic acids in studies aimed at determining the utility of HDAC inhibitors as memory enhancers and mood stabilizers.
摘要
将具有已知中枢神经系统和组蛋白脱乙酰酶（HDAC）抑制活性的羧酸转化为异羟肟酸，并使用一系列针对重组HDAC亚型的体外生化测定法、人宫颈癌Hela细胞和小鼠前脑原代培养物中的细胞测定法以及全动物（非洲爪蟾）发育测定法进行测试。相对于母体羧酸，其中两种类似物表现出增强的效力，一种类似物在非洲爪蟾测定中显示出改变的HDAC亚型选择性和体内活性。我们讨论了这些新型异羟肟酸在旨在确定HDAC抑制剂作为记忆增强剂和情绪稳定剂效用的研究中的潜在用途。
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