Characterization of a genetically engineered inactivation- resistant coagulation factor VIIIa

Steven W. Pipe; Randal J. Kaufman

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Characterization of a genetically engineered inactivation- resistant coagulation factor VIIIa

机译：基因工程抗失活凝血因子VIIIa的表征

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Individuals with hemophilia A require fre- quent infusion of preparations of coagulation factor VIII. The activity of factor VIII (FVIII) as a cofactor for factor IXa in the coagulation cascade is limited by its instability after activation by thrombin. Activation of FVIII occurs through proteolytic cleav- age and generates an unstable FVIII heterotrimer that is subject to rapid dissociation of its subunits. In addition, further proteo- lytic cleavage by thrombin, factor Xa, factor IXa, and activated protein C can lead to inactivation. We have engineered and characterized a FVIII protein, IR8, that has enhanced in vitro stability of FVIII activity due to resistance to subunit dissociation and proteolytic inactivation.

机译：患有A型血友病的患者需要经常输注凝血因子VIII的制剂。在凝血级联反应中，凝血因子VIII（FVIII）作为凝血因子IXa的辅助因子的活性受到其不稳定性的限制。 FVIII的活化通过蛋白水解切割发生，并产生不稳定的FVIII异源三聚体，该异源三聚体会快速分解其亚基。另外，凝血酶，Xa因子，IXa因子和活化的蛋白C进一步的蛋白水解切割可能导致失活。我们已经设计并鉴定了一种FVIII蛋白IR8，由于对亚基解离和蛋白水解失活具有抗性，因此具有增强的FVIII活性体外稳定性。

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《Proceedings of the National Academy of Sciences of the United States of America》 |1997年第22期|p.11851-11856|共6页
作者
Steven W. Pipe; Randal J. Kaufman;
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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种 eng
中图分类自然科学总论;
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6. Characterization of a genetically engineered inactivation-resistant coagulation factor VIIIa [O] . Steven W. Pipe, Randal J. Kaufman 1997

机译：基因工程抗失活凝血因子VIIIa的表征
7. Characterization of a genetically engineered inactivation-resistant coagulation factor VIIIa [O] . S. W. Pipe, R. J. Kaufman 1997

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Characterization of a genetically engineered inactivation- resistant coagulation factor VIIIa

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