Modified thrombin receptor-agonist peptide ligands. Synthesis and conformational analysis of analogs of the N-terminal tripeptide region

✍ Scribed by Tetsuo Shimamoto; Hiroko Tsuboi; Yasuo Kitajima; Tomoko Miyazaki; Yoshiaki Oyama; Seiichi Imajo; Masaji Ishiguro

• Book ID: 103983116
• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 365 KB
• Volume: 5
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00421-o

✦ Synopsis

Analogs 2-24 of the N-terminal tripeptide region of the tethered peptide ligand for human thrombin receptor have been synthesized for elucidation of the receptor bound conformation of the ligand peptide and the conformational analysis of model structures 25-30 of those peptide analogs suggested a plausible conformation for the receptor bound structure of the tripeptide region.

A serine protease thrombin activates a variety of cells such as platelets, endothelial cells and vascular smooth muscle through proteolytic cleavage of the extracellular N-terminus bond between Arg41 and Ser42 of human thrombin receptor. 1-3 The newly generated N-terminal region then functions as a "tethered ligand", probably interacting with an, as yet, unidentified site in the remaining extracellular sites or the transmembrane region of the receptor. In support of this activation model, antibodies which recognize the cleavage site have inhibited the effects of thrombin 4-7 and peptides having the N-terminal 14 residues have been shown to act as agonist ligands on the thrombin receptor, l Since Vu et al showed the activity of the N-terminal tetradecapeptide as a ligand peptide for the thrombin