The design of synthetic inhibitors of thrombin
- 256 páginas
- 9 horas de lectura
In one generation, blood coagulation factors have evolved into distinct protein entities, isolated in pure form, expressed through recombinant DNA techniques, and analyzed using modern physical chemistry methods such as X-ray diffraction, NMR, ESR, and fluorescence spectroscopy. A significant milestone was achieved in 1989 by W. Bode, R. Huber, and their team with the determination of the crystal structure of human α-thrombin, inhibited with D-Phe-Pro-Arg chloromethyl ketone. This structure greatly aids in understanding the interatomic interactions between thrombin and its substrates, particularly fibrinogen, while also providing a foundation for designing thrombin inhibitors, which is the focus of this symposium. The event was organized into four sessions: (1) Structural features of thrombin interactions, (2) Synthetic inhibitors, (3) Hirudin and its analogues, and (4) Pharmacological and clinical considerations. This book includes summaries of most presentations and complements two previous volumes that offer a comprehensive overview of thrombin: the 1977 edition "Chemistry and Biology of Thrombin" and the 1992 edition "Thrombin: Structure and Function."
