Non-Immunogenic Peptide Anticoagulant

非免疫原性肽抗凝剂

• 批准号: 6691111
• 负责人: DAVID Henry FARRELL
• 金额: $ 10万
• 依托单位: BARLOW SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-20 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691111
• 关键词: anticoagulants; biomaterial development /preparation; clinical research; heparin; human tissue; peptides; platelets; protein isoforms

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.

我们已经鉴定出一种新的肝素样肽类凝血抑制物，它是一种多肽 自然产生的人类纤维蛋白原亚型--伽马A/伽马‘纤维蛋白原的片段。这种多肽在整个血浆中具有抗凝活性，不太可能引起免疫反应，因为它是这种纤维蛋白原亚型的正常纤溶裂解产物。本文重点介绍了该多肽作为一种潜在的药理抗凝剂的研究进展。这种多肽抗凝剂与肝素相比具有显著的优势，可以作为肝素的一般替代品，特别是在肝素临床禁忌的情况下，如肝素引起的血小板减少症。因此，具体目标是： I)在重组表达系统中表达所述γ‘链肽。 Ii)检测重组Gamma1‘肽的抗凝血活性和抗血小板活性。 在这些研究结束时，第二阶段将达到重要的里程碑。 伽马肽作为药理抗凝剂的研究进展。