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型肝素样肽基凝血抑制剂，它是一种肽 天然存在的人类纤维蛋白原同工型 gammaA/gamma' 纤维蛋白原的片段。该肽在全血浆中具有抗凝活性，并且不太可能引起免疫反应，因为它是该纤维蛋白原亚型的正常纤溶裂解产物。本申请的重点是开发这种肽作为潜在的药理抗凝剂。这种肽抗凝剂比肝素具有显着的优势，并且可以用作肝素的通用替代品，特别是当肝素临床禁忌时，如肝素诱导的血小板减少症的情况。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γ1,'肽的抗凝血和抗血小板活性。 这些研究结束后，第二阶段将实现重要的里程碑 开发γ'肽作为药理抗凝剂。