Novartis Institutes for Biomedical Research, 100 Technology Square & 250 Massachusetts Avenue, Cambridge, MA 02139, USA.
Bioorg Med Chem. 2011 Aug 1;19(15):4626-34. doi: 10.1016/j.bmc.2011.06.030. Epub 2011 Jun 15.
Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.
在此，我们报告了一类新型的、简单的、源于氨基酸的 I 类组蛋白去乙酰化酶抑制剂的发现，这类抑制剂通过进入内部乙酸盐释放通道来表现出同工酶选择性。同工酶选择性标准是基于这些新型抑制剂与 HDAC8 结合的 X 射线晶体学和分子建模来讨论的，这可能通过在原子水平上揭示的新结构特征来深入了解酶功能的机制。
