Development of a Selective Peptide Macrocycle Inhibitor of Coagulation Factor XII toward the Generation of a Safe Antithrombotic Therapy

被引：50

作者：

Baeriswyl, Vanessa ^{[1
]}

Calzavarini, Sara ^{[2
]}

Gerschheimer, Christiane ^{[2
]}

Diderich, Philippe ^{[1
]}

Angelillo-Scherrer, Anne ^{[2
]}

Heinis, Christian ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, Inst Chem Sci & Engn, CH-1015 Lausanne, Switzerland

[2] Univ Lausanne Hosp, Serv & Cent Lab Hematol, CH-1011 Lausanne, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 56卷 / 09期

基金：

瑞士国家科学基金会;

关键词：

ACTIVATED HAGEMAN-FACTOR; THROMBUS FORMATION; TRYPSIN; SEQUENCE; POTENT;

D O I：

10.1021/jm400236j

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inhibition of coagulation factor XII (FXII) activity represents an attractive approach for the treatment and prevention of thrombotic diseases. The few existing FXII inhibitors suffer from low selectivity. Using phage display combined to rational design, we developed a potent inhibitor of FXII with more than 100-fold selectivity over related proteases. The highly selective peptide macrocycle is a promising candidate for the control of FXII activity in antithrombotic therapy and a valuable tool in hematology research.

引用

页码：3742 / 3746

页数：5

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