HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF
HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF
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DOI：
10.1016/s1097-2765(00)80452-9
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发表时间：
2000-03-01
期刊：
影响因子：
16
通讯作者：
Cole, PA
中科院分区：
文献类型：
--
作者：
Lau, OD;Kundu, TK;Cole, PA
组蛋白乙酰转移酶（HATs）在基因表达调控中起重要作用。在本报告中，我们描述了肽 - 辅酶A偶联物作为转录辅激活因子p300和PCAF的选择性HAT抑制剂的设计、合成及应用。发现两种抑制剂（针对p300的Lys - CoA和针对PCAF的H3 - CoA - 20）在阻断p300和PCAF的HAT活性方面具有强效（半数抑制浓度约为0.5 μM）且具有选择性（约200倍）。这些抑制剂被用于在几种检测系统中探究HAT功能的酶学和转录特性。这些化合物作为生物学工具，在转录研究中评估HATs的作用方面应具有广泛用途，并且可作为开发新型抗肿瘤治疗药物的先导化合物。
Histone acetyltransferases (HATs) play important roles in the regulation of gene expression. In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for PCAF) were found to be potent (IC50 approximate to 0.5 mu M) and selective (similar to 200-fold) in blocking p300 and PCAF HAT activities. These inhibitors were used to probe enzymatic and transcriptional features of HAT function in several assay systems. These compounds should be broadly useful as biological tools for evaluating the roles of HATs in transcriptional studies and may serve as lead agents for the development of novel antineoplastic therapeutics.