title: Substrate-Guided Design of Selective FXIIa Inhibitors Based on the Plant-Derived Momordica cochinchinensis Trypsin Inhibitor-II (MCoTI-II) Scaffold.
abstract: 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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Joakim E
authors.initials: JE
authors.lastname: Swedberg
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Tunjung
authors.initials: T
authors.lastname: Mahatmanto
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Hafiza
authors.initials: H
authors.lastname: Abdul Ghani
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane Queensland 4059, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: de Veer
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Schroeder
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology , Brisbane Queensland 4059, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Harris
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D001798:Blood Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015956:Factor XIIa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D029775:Momordica / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001798:Blood Proteins; D009842:Oligopeptides; C053635:factor XIIa inhibitor; D015956:Factor XIIa