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

页码：3117 / 3122

页数：6

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