晶体学和构效关系分析揭示了选择性且强效抑制SIRT2去乙酰化酶和癸酰化酶所需的高要求。
Crystallographic and SAR analyses reveal the high requirements needed to selectively and potently inhibit SIRT2 deacetylase and decanoylase.
作者信息
Yang Ling-Ling, Xu Wei, Yan Jie, Su Hui-Lin, Yuan Chen, Li Chao, Zhang Xing, Yu Zhu-Jun, Yan Yu-Hang, Yu Yamei, Chen Qiang, Wang Zhouyu, Li Lin, Qian Shan, Li Guo-Bo
机构信息
College of Food and Bioengineering , Xihua University , Sichuan 610039 , China . Email:
Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education , Department of Medicinal Chemistry , West China School of Pharmacy , Sichuan University , Chengdu 610041 , China . Email:
出版信息
Medchemcomm. 2018 Dec 7;10(1):164-168. doi: 10.1039/c8md00462e. eCollection 2019 Jan 1.
Abstract
A high-quality X-ray crystal structure reveals the mechanism of compound inhibiting SIRT2 deacetylase and decanoylase. Structure-activity relationship (SAR) analysis of the synthesized derivatives of reveals the high requirements needed for selective inhibitors to bind with the induced hydrophobic pocket and potently inhibit sirtuin 2 deacetylase.
摘要
高质量的X射线晶体结构揭示了化合物抑制SIRT2脱乙酰酶和癸酰化酶的机制。对该化合物合成衍生物的构效关系（SAR）分析表明，选择性抑制剂与诱导产生的疏水口袋结合并有效抑制沉默调节蛋白2脱乙酰酶需要满足很高的条件。
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