Anticoagulant peptides: nature of the interaction of the C-terminal region of hirudin with a noncatalytic binding site on thrombin.

摘要: A series of 20 C-terminal fragment analogues the anticoagulant peptide hirudin were synthesized by solid-phase techniques in order to investigate nature thrombin-hirudin interaction. Inhibition plasma fibrin clot formation thrombin vitro was used as a measure activity. In minimum region necessary for detectable activity, hirudin56-64, positions Phe56, Glu57, Ile59, Pro60, and Leu64 are sensitive modification. These residues apparently important direct interaction with or maintaining favorable conformation On basis conformational analysis this computational methods, "kinked" amphipathic alpha-helical structure, which orients all most critical activity on one face helix, is proposed.