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Details of the crystal structure of human thrombin in complex with the central part of human fibrin are revealed and results are presented of the molecular modeling of the fibrinopeptides A and B (fpA- and fpB-) containing portions of the Aalpha and Bbeta chains, in both fibrinogen and protofibrils. Analysis provides a coherent rationale for the preferential removal of fpA from fibrinogen at the first stage of fibrin assembly and the accelerated cleavage of fpB from protofibrils at the second stage.

The design and synthesis of a new core structure, a ring-oxygenated variant of 2-carboxy-6-hydroxyoctahydroindole (Choi) from D-glucose is reported. The ring-oxygenated variant of 2-carboxy-6-hydroxyoctahydroindole can potentially be used as a surrogate of Choi in the design and synthesis of aeruginosin-based thrombin inhibitors.

A study was conducted to examine that N[a.sub.+]-binding and exosite-1 are linked to eachother. Findings reveal that while exosite-2 of thrombin is an independent cofactor binding-site, both N[a.sub.+]-binding and exosite-1 are linked to eachother.

A simple strategy to prepare aptamer-based ligands with enhanced binding affinities and the anticlotting activities of thrombin bivalent ligands is described. The two aptamer ligands with suboptimal binding properties are covalently linked with a long flexible linker to create a bivalent ligand with significantly improved binding affinity.

The effect of mutations in thrombomodulin on protein C activation and thrombin binding is studied. These mutations are ineffective in altering the steady state fluorescence of fluorescein-EGR-chloromethylketone present in the active site of thrombin and decreased the rate or protein C activation.

Evidence that electrospray ionization (ESI) MS detects the formation of G-quadruplex of the thrombin-binding aptamer in solution is reported, and some of its properties in the gas phase are established, especially its specific interaction with metal ions. The lack of a smooth correlation between the ionic radii and the extent of adduct formation for metal ions suggest that the size of the metal ions is not the only factor in stabilizing the intramolecular G-quadruplex structure.