Analysis of Subpocket Selectivity and Identification of Potent Selective Inhibitors for Matriptase and Matriptase-2

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• 作者：Dominic Duch锚ne ; Elo茂c Colombo ; Antoine D茅silets ; Pierre-Luc Boudreault ; Richard Leduc ; Eric Marsault ; Rafael Najmanovich
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：December 11, 2014
• 年：2014
• 卷：57
• 期：23
• 页码：10198-10204
• 全文大小：306K
• ISSN：1520-4804

文摘

We studied the factors affecting the selectivity of peptidomimetic inhibitors of the highly homologous proteases matriptase and matriptase-2 across subpockets using docking simulations. We observed that the farther away a subpocket is located from the catalytic site, the more pronounced its role in selectivity. As a result of our exhaustive virtual screening, we biochemically validated novel potent and selective inhibitors of both enzymes.