期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 58, 期 16, 页码 6630-6638出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b00845
关键词
-
资金
- Australian Research Council [DP110100071, FT10100185]
- EU
- National Institutes of Health [CA165284]
Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study, we present five X-ray crystal structures, determined to a resolution of 1.7 angstrom or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically map key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据