Swedberg Joakim E, Mahatmanto Tunjung, Abdul Ghani Hafiza, de Veer Simon J, Schroeder Christina I, Harris Jonathan M, Craik David J
Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane Queensland 4059, Australia.
J Med Chem. 2016 Aug 11;59(15):7287-92. doi: 10.1021/acs.jmedchem.6b00557. Epub 2016 Aug 1.
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.
血栓形成是心血管疾病相关发病和死亡的主要原因。抑制因子XIIa（FXIIa）可提供血栓保护且无出血并发症。在此，我们确定了FXIIa及其紧密同源物因子Xa的扩展底物特异性，并利用这些数据，结合基于抑制剂和结构导向的方法，设计基于罗汉果胰蛋白酶抑制剂-II的选择性FXIIa抑制剂。
