Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes

被引：13
|
作者：
Ghosh, Arun K. [1 ,2 ]
Reddy, Bhavanam Sekhara [1 ,2 ]
Yen, Yu-Chen [3 ]
Cardenas, Emilio L. [1 ,2 ]
Rao, Kalapala Venkateswara [1 ,2 ]
Downs, Deborah [5 ]
Huang, Xiangping [5 ]
Tang, Jordan [5 ]
Mesecarabc, Andrew D. [1 ,2 ,3 ,4 ]
机构：
[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[2] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA
[3] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA
[4] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA
[5] Univ Oklahoma, Oklahoma Med Res Fdn, Prot Studies Program, Oklahoma City, OK 73104 USA
来源：
CHEMICAL SCIENCE | 2016年 / 7卷 / 05期
基金：
美国国家卫生研究院;
关键词：
CATHEPSIN-D; ASPARTIC PROTEASE; BACE2; GLUCOSE; SPECIFICITY; SITE;
D O I：
10.1039/c5sc03718b
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Design, synthesis and evaluation of very potent and selective beta-secretase 2 (memapsin 1, BACE 2) inhibitors are described. The inhibitors were designed specifically to interact with the S20-site of beta-secretase 2 to provide >170 000-fold selectivity over beta-secretase (BACE 1) and >15 000-fold selectivity over cathepsin D. BACE 2 is implicated in type 2 diabetes. The studies serve as an important guide to selective BACE 2 inhibitors.
引用
收藏
页码：3117 / 3122
页数：6
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