Different roles of two consecutive leucine residues in a receptor-tethered ligand peptide (SFLLRNP) in thrombin receptor activation

T. Nose, Y. Shimohigashi, M. Okazaki, Y. Satoh, T. Costa, N. Shimizu, Y. Ogino, M. Ohno

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A synthetic peptide, H-Ser-Phe-Leu-Leu-Arg-Asn-Pro-NH2, which corresponds to a ligand peptide tethered to a human thrombin receptor, was able to activate the thrombin receptor with no thrombin. In order to inspect the structural requisites of two consecutive leucines (Leu-3 and Leu-4) in receptor activation, two sets of analogs with substitutions at either position 3 or 4 were synthesized and evaluated for their ability to hydrolyze phosphoinositide in human neuroblastoma SH-EP cells. The replacement of Leu-4 by Ala drastically decreased the activity of the parent peptide (only about 4% activity), while that of Leu-3 retained about 50% activity. A similar result was obtained when replaced by Gly. Substitution by Phe for Leu-3 sustained full activity. Although the Leu-4/Phe substitution exhibited a slight reduction in activity, Leu-4/Ile substitution unexpectedly diminished the activity (20%). These results suggested that two consecutive leucines have different roles in receptor activation; i.e., Leu-3 behaves something like a connection of peptide units to construct a bioactive conformation and Leu-4 acts like a structural element essential for interactions with receptors.

Original languageEnglish
Pages (from-to)2695-2698
Number of pages4
JournalBulletin of the Chemical Society of Japan
Volume68
Issue number9
DOIs
Publication statusPublished - Sep 1995

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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