The Role of Arginine in Thrombin Receptor Tethered-Ligand Peptide in Intramolecular Receptor Binding and Self-Activation

Access this Article

Search this Article



Synthetic heptapeptide of the human thrombin receptor tethered-ligand peptide, H–Ser–Phe–Leu–Leu–Arg–Asn–Pro–NH<sub>2</sub> (SFLLRNP), activates fully the thrombin receptor without thrombin. The functional role of Arg-5 was examined using a series of analogs having amino acid substitutions at position 5 in this assays was to assess the abilities to hydrolyze phosphoinositide in human neuroblastoma SH-EP cells and to aggregate the human platelet. The replacement of Arg-5 by Ala reduced the activity (9% activity of the parent peptide) in the PI-turnover assay, and abolished completely the platelet aggregation activity. SFLL/Lys/NP was also active, but moderately: 36% in PI-turnover and 12% in platelet aggregation. These results indicated that the electrostatic interaction of the Arg-guanidino group is important for a peptide to interact with the receptor. When citrulline or glutamine was placed at position 5 instead of arginine, the resulting SFLL/citrulline/NP and SFLL/Gln/NP were found to be potent in both assays. Since citrulline and glutamine possess a side chain which can serve as hydrogen donor and/or acceptor, the receptor activation of these peptides appears to be due to hydrogen bonding at this position. The molecular mechanisms to explain both electrostatic and hydrogen-bonding interactions were postulated based on the structural modeling of seven-transmembrane domain thrombin receptor.


  • Bulletin of the Chemical Society of Japan

    Bulletin of the Chemical Society of Japan 71(7), 1661-1665, 1998-07-15

    The Chemical Society of Japan

References:  21

Cited by:  2


  • NII Article ID (NAID)
  • Text Lang
  • Article Type
    Journal Article
  • ISSN
  • NDL Article ID
  • NDL Source Classification
  • NDL Call No.
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top