Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Bioorg Med Chem Lett. 2012 Aug 1;22(15):5025-30. doi: 10.1016/j.bmcl.2012.06.017. Epub 2012 Jun 18.
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.
报道了一系列新型光反应性苯甲酰胺探针用于 I 类组蛋白去乙酰化酶（HDAC）同工型的设计、建模、合成和生物评价。这些探针对 HDAC1 和 2 具有很强的选择性和效力，并且在光标记实验中能够有效地与 HDAC2 交联。探针表现出对 I 类 HDAC 的时间依赖性抑制作用。探针的抑制活性受到芳基和烷基叠氮基团定位的影响，这些基团对于光交联和生物素标签的附着是必需的。探针抑制了 MDA-MB-231 细胞系中 H4 的去乙酰化，表明它们具有细胞通透性，并靶向核 HDAC。
