Design, synthesis, modeling, biological evaluation and photoaffinity labeling studies of novel series of photoreactive benzamide probes for histone deacetylase 2.
Design, synthesis, modeling, biological evaluation and photoaffinity labeling studies of novel series of photoreactive benzamide probes for histone deacetylase 2.
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用于组蛋白脱乙酰酶 2 的新型光反应性苯甲酰胺探针系列的设计、合成、建模、生物学评估和光亲和标记研究。
DOI：
10.1016/j.bmcl.2012.06.017
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发表时间：
2012
影响因子：
2.7
通讯作者：
Petukhov,PavelA
中科院分区：
文献类型：
--
作者：
Vaidya,AdityaSudheer;Karumudi,Bhargava;Mendonca,Emma;Madriaga,Antonett;Abdelkarim,Hazem;vanBreemen,RichardB;Petukhov,PavelA
报道了一系列新型的光反应性苯甲酰胺类HDAC异构体探针的设计、建模、合成和生物学评价。光标记实验表明，该探针对HDAC1和HDAC2具有较强的选择性，并能有效地与HDAC2发生交联反应。这些探针显示出对I类HDAC的时间依赖的抑制。探针的抑制活性受生物素标记光交联所必需的芳基和烷基叠氮基团位置的影响。这些探针抑制了MDA-MB-231细胞中H4的脱乙酰化，表明它们是细胞通透性的，并以核HDAC为靶点。
The design, modeling, synthesis, biological evaluation of a novel series of photoreactive benzamide probes for class I HDAC isoforms is reported. The probes are potent and selective for HDAC1 and 2 and are efficient in crosslinking to HDAC2 as demonstrated by photolabeling experiments. The probes exhibit a time-dependent inhibition of class I HDACs. The inhibitory activities of the probes were influenced by the positioning of the aryl and alkyl azido groups necessary for photocrosslinking and attachment of the biotin tag. The probes inhibited the deacetylation of H4 in MDA-MB-231 cell line, indicating that they are cell permeable and target the nuclear HDACs.