BLOOD CLOTTING PROTEINS: FIBRINOGEN & CLOTTING FACTORS

凝血蛋白：纤维蛋白原

• 批准号: 6120581
• 负责人: Michael W Mosesson
• 金额: $ 2.38万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6120581
• 关键词: biomedical resource; genetics; hematology; proteins

The original fibrinogen study is one of our oldest collaborations. A human mutation produces a hemophilia due to a single amino acid change in fibrinogen called fibrinogen Metz. We labeled this site with Au, , and localized it to high resolution with the STEM. Other studies label the non-covalen0epolymerization sites on fibrinogen by synthesizing the tetrapeptide that binds there and adding a cysteine for gold attachment This pentapeptide also specifically targets the"epolymerization site and has now been Au-labeled to structurally map this site. This demonstrates the power of these techniques to map important functional subrnolecular sites and domain at high resolution. . We are also studying intermediates in the formation of fibrin polymers using fibrinogen modified in various ways or labeled with clusters. A paper on early intermediates in fibrin polymerization has been published.': Nanogold has been used to label thrombin to map its binding site(s) on fibrinogen. The labeling has been good, but excess gold has been difficult to remove so the mapping is still inconclusive. Factor VM is what is defective in hemophilia. Baxter Healthcare has it cloned in different expression systems. They am interested in compared the factor VHI from these systems with the one from human plasma.

最初的纤维蛋白原研究是我们最古老的合作之一。 人类突变会导致血友病，原因是单一的氨基酸 纤维蛋白原的变化称为纤维蛋白原甲基。我们给这个网站贴上了标签 使用Au，并使用STEM将其局部化到高分辨率。其他 纤维蛋白原上非共价烯聚合点的标记研究 合成与其结合的四肽并添加半胱氨酸 对于黄金附着物，该五肽还特别针对 聚合点，现在已经被Au标记到结构上 绘制此站点的地图。这展示了这些技术在地图绘制中的威力 重要的功能亚分子位点和结构域 决议。。我们也在研究中间体的形成。 使用纤维蛋白原以不同方式修饰或标记的纤维蛋白聚合物 有集群的。一篇关于纤维蛋白的早期中间体的论文 聚合已发表。纳米金已被用来标记 凝血酶将其结合部位(S)定位在纤维蛋白原上。标签上有 很好，但过多的黄金很难移除，所以地图 仍然没有定论。在血友病中，Vm因子存在缺陷。 Baxter Healthcare将其克隆到不同的表达系统中。他们 我感兴趣的是将这些系统中的VHI因子与 一种来自人类血浆。