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 Au11 and localized it to high resolution with the STEM. Other studies label the non-covalent TMa"""""""" polymerization sites on fibrinogen by synthesizing the tetrapeptide that binds there and adding a cysteine for gold attachment. This pentapeptide also specifically targets the 11a'9 polymerization site and has now been Au-labeled to structurally map this site. This demonstrates the power of these techniques to map important ~nctionai submolecular sites and domains 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 submitted. 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.
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