THROMBUS DETECTION USING FIBRIN-SPECIFIC ANTIBODIES

使用纤维蛋白特异性抗体检测血栓

• 批准号: 3339435
• 负责人: GARY R MATSUEDA
• 金额: $ 22.51万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3339435
• 关键词: aminoacid analyzer; antibody specificity; antigens; binding proteins; cardiovascular disorder diagnosis; crosslink; diagnosis design /evaluation; diagnosis quality /standard; disease /disorder model; embolism; fibrin; fibrinogen; high performance liquid chromatography; hybridomas; immunization; immunochemistry; immunoconjugates; immunohematology; immunologic techniques; immunotherapy; laboratory mouse; laboratory rabbit; mass spectrometry; monoclonal antibody; noninvasive diagnosis; peptide analog; peptide chemical synthesis; protein sequence; radionuclide diagnosis; radionuclide imaging /scanning; radiopharmacology; synthetic peptide; thrombosis

Current methods for in vivo thrombus detection either lack specificity or pose additional health risks. With the tools of molecular immunology and syntheitic peptide chemistry, we plan to prepare a clinically useful, diagnostic antibody that possesses specificity for human fibrin (the structural protein in thrombi) and provides sufficient sensitivity for in vivo thrombus detection by gamma scintigraphy. Our strategy will emphasize the differences between fibrin and its soluble precursor, fibrinogen, and will focus on ways to select fibrinspecific antibodies. Synthetic peptides will be designed to mimic fibrinunique epitopes and used to elicit antibodies that will bind human fibrin in the presence of fibrinogen. This approach was validated during the previous grant period when we used a synthetic peptide corresponding to the N terminus of the human fibrin beta-chain to elicit monoclonal antibodies that bound to fibrin monomer in the presence of fibrinogen. The in vivo specificity of one monoclonal antibody (64C5) was confirmed in experiments using chicken, rabbit and dog models. In the research proposed here, we focus on the design and testing of various fibrin-like peptides corresponding to thrombin cleavage sites and Factor XIIIa cross-link sites, and describe plans for an improved screening strategy that uses fibrin miniclots rather than fibrin monomers as antigens. Our specific aims include the in vivo testing of antibody 5D7 as a gamma scintigraphic agent for detecting experimental thrombi; the preparation of monoclonal antibodies that avidly bind to clotted fibrin; the synthesis and refinement of cross-link antigens related to gamma-chain cross-link sites; and the structural and immunochemical study of the alpha-chain cross-link site in order to identify a new fibrin-unique epitope. Three specific benefits will result from these experiments: First, they will provide a detailed immunochemical analysis of unique epitopes on the fibrin molecule. They will also suggest general methods for differentiating any protein from its precursor. Second, they will provide reagents that can tag thrombi in vivo. Third, they will lay the foundation upon which a sensitive and specific noninvasive test for life-threatening thromboembolism can be built.

目前体内血栓检测方法缺乏

项目成果

The AGDV residues on the gamma chain carboxyl terminus of platelet-bound fibrinogen are needed for platelet aggregation.

血小板结合纤维蛋白原的 γ 链羧基末端上的 AGDV 残基是血小板聚集所必需的。

• DOI: 10.1016/s0167-4838(97)00130-1
• 发表时间: 1997
• 期刊: Biochimica et biophysica acta
• 作者: Liu,Q;Matsueda,G;Brown,E;Frojmovic,M
• 通讯作者: Frojmovic,M

Immunodetection of human fibrin using monoclonal antibody-64C5 in an extracorporeal chicken model.

在体外鸡模型中使用单克隆抗体 64C5 进行人纤维蛋白的免疫检测。

• 发表时间: 1985
• 期刊: Thrombosis and haemostasis
• 影响因子: 6.7
• 作者: Hui,KY;Haber,E;Matsueda,GR
• 通讯作者: Matsueda,GR

Bispecific Monoclonal Antibodies Produced by Somatic Cell Fusion Increase the Potency of Tissue Plasminogen Activator

体细胞融合产生的双特异性单克隆抗体可提高组织纤溶酶原激活剂的效力

• DOI: 10.1055/s-0038-1647297
• 发表时间: 1990
• 期刊: Thrombosis and Haemostasis
• 影响因子: 6.7
• 作者: E. Branscomb;M. Runge;C. Savard;Keith Adams;G. Matsueda;E. Haber
• 通讯作者: E. Haber

Characterization of a monoclonal antibody directed against the carboxyl-terminus of human factor XIII. An epitope exposed upon denaturation and conserved across species lines.

针对人因子 XIII 羧基末端的单克隆抗体的表征。

• 发表时间: 1994
• 期刊: Thrombosis and haemostasis
• 影响因子: 6.7
• 作者: Song,Y;Taubenfeld,SM;Sheng,D;Matsueda,GR
• 通讯作者: Matsueda,GR

Acceleration of plasma clot lysis by an antibody to alpha 2-antiplasmin.

α2-抗纤溶酶抗体加速血浆凝块溶解。

• 发表时间: 1988
• 期刊: Transactions of the Association of American Physicians
• 作者: Reed3rd,GL;Matsueda,GR;Haber,E
• 通讯作者: Haber,E