Substrate-Guided Design of Selective FXIIa Inhibitors Based on the Plant-Derived Momordica cochinchinensis Trypsin Inhibitor-II (MCoTI-II) Scaffold
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- 作者：Joakim E. Swedberg ; Tunjung Mahatmanto ; Hafiza Abdul Ghani ; Simon J. de Veer ; Christina I. Schroeder ; Jonathan M. Harris ; David J. Craik
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：August 11, 2016
- 年：2016
- 卷：59
- 期：15
- 页码：7287-7292
- 全文大小：331K
- 年卷期：0
- ISSN：1520-4804
文摘
Thrombosis is a leading cause of morbidity and mortality associated with cardiovascular diseases. Inhibition of factor XIIa (FXIIa) provides thrombus protection without bleeding complications. Here, we defined the extended substrate specificity of FXIIa and its close homologue factor Xa and used these data, together with inhibitor-based and structure-guided methods, to engineer selective FXIIa inhibitors based on Momordica cochinchinensis trypsin inhibitor-II.