BLOOD CLOTTING PROTEINS: FIBRINOGEN & CLOTTING FACTORS

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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.