Non-Immunogenic Peptide Anticoagulant

我们已经确定了一种新的肝素样肽基凝血抑制剂， 天然存在的人纤维蛋白原同种型γ A/γ ′纤维蛋白原的片段。该肽在整个血浆中作为抗凝剂是有活性的，并且不太可能引起免疫应答，因为它是该纤维蛋白原同种型的正常纤维蛋白溶解裂解产物。本申请的重点是开发这种肽作为一种潜在的药理学抗凝剂。这种肽抗凝剂与肝素相比具有显著的优势，并且可以用作肝素的一般替代品，特别是当肝素在临床上是禁忌时，如在肝素诱导的血小板减少症的情况下。因此，具体目标是： I）在重组表达系统中表达γ '链肽。 II）测定重组γ 1肽的抗凝血和抗血小板活性。 在这些研究结束时，将实现II期的重要里程碑 γ肽作为药理学抗凝剂的开发。

We have identified a novel heparin-like peptidyl coagulation inhibitor that is a peptide fragment of a naturally-occurring human fibrinogen isoform, gammaA/gamma' fibrinogen. The peptide is active as an anticoagulant in whole plasma, and is unlikely to elicit an immune response, since it is a normal fibrinolytic cleavage product of this fibrinogen isoform. This application focuses on the development of this peptide as a potential pharmacologic anticoagulant. This peptide anticoagulant would have significant advantages over heparin, and could be used as a general replacement for heparin, particularly when heparin is clinically contraindicated, as in cases of heparin-induced thrombocytopenia. The specific aims are therefore to: I) Express the gamma' chain peptide in a recombinant expression system. II) Assay the recombinant gamma1,' peptide for anticoagulant and anti-platelet activities. At the conclusion of these studies, essential milestones will be achieved for Phase II development of the gamma' peptide as a pharmacologic anticoagulant.