Substrate-Guided Design of Selective FXIIa Inhibitors Based on the Plant-Derived Momordica cochinchinensis Trypsin Inhibitor-II (MCoTI-II) Scaffold

Joakim E. Swedberg; Tunjung Mahatmanto; Hafiza Abdul Ghani; Simon J. De Veer; Christina I. Schroeder; Jonathan M. Harris; David J. Craik

doi:10.1021/acs.jmedchem.6b00557

Substrate-Guided Design of Selective FXIIa Inhibitors Based on the Plant-Derived Momordica cochinchinensis Trypsin Inhibitor-II (MCoTI-II) Scaffold

Joakim E. Swedberg
, Tunjung Mahatmanto
, Hafiza Abdul Ghani
, Simon J. De Veer
, Christina I. Schroeder
, Jonathan M. Harris
, David J. Craik^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

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.

Original language	English
Pages (from-to)	7287-7292
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	59
Issue number	15
DOIs	https://doi.org/10.1021/acs.jmedchem.6b00557
Publication status	Published - 11 Aug 2016
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1021/acs.jmedchem.6b00557

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@article{62da96d6dad34af999b06dc1c8c20428,

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.",

author = "Swedberg, \{Joakim E.\} and Tunjung Mahatmanto and \{Abdul Ghani\}, Hafiza and \{De Veer\}, \{Simon J.\} and Schroeder, \{Christina I.\} and Harris, \{Jonathan M.\} and Craik, \{David J.\}",

note = "Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

month = aug,

day = "11",

doi = "10.1021/acs.jmedchem.6b00557",

language = "English",

volume = "59",

pages = "7287--7292",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "15",

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TY - JOUR

T1 - Substrate-Guided Design of Selective FXIIa Inhibitors Based on the Plant-Derived Momordica cochinchinensis Trypsin Inhibitor-II (MCoTI-II) Scaffold

AU - Swedberg, Joakim E.

AU - Mahatmanto, Tunjung

AU - Abdul Ghani, Hafiza

AU - De Veer, Simon J.

AU - Schroeder, Christina I.

AU - Harris, Jonathan M.

AU - Craik, David J.

PY - 2016/8/11

Y1 - 2016/8/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84982085136

U2 - 10.1021/acs.jmedchem.6b00557

DO - 10.1021/acs.jmedchem.6b00557

M3 - Article

C2 - 27434175

AN - SCOPUS:84982085136

SN - 0022-2623

VL - 59

SP - 7287

EP - 7292

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 15

ER -

Substrate-Guided Design of Selective FXIIa Inhibitors Based on the Plant-Derived Momordica cochinchinensis Trypsin Inhibitor-II (MCoTI-II) Scaffold

Abstract

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