Development of a Selective Peptide Macrocycle Inhibitor of Coagulation Factor XII toward the Generation of a Safe Antithrombotic Therapy
Development of a Selective Peptide Macrocycle Inhibitor of Coagulation Factor XII toward the Generation of a Safe Antithrombotic Therapy
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DOI：
10.1021/jm400236j
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发表时间：
2013-05-09
影响因子：
7.3
通讯作者：
Heinis, Christian
中科院分区：
文献类型：
--
作者：
Baeriswyl, Vanessa;Calzavarini, Sara;Heinis, Christian
抑制凝血因子XII(FXII)活性是治疗和预防血栓性疾病的一种有吸引力的方法。现有的为数不多的FXII抑制剂存在选择性低的问题。利用噬菌体展示结合合理的设计，我们开发了一种有效的FXII抑制剂，其对相关蛋白酶的选择性超过100倍。高选择性多肽大环在抗血栓治疗中控制FXII活性是一种有前景的候选药物，在血液学研究中也是一种有价值的工具。
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.