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Thromb Haemost 2000; 83(01): 165-170
DOI: 10.1055/s-0037-1613773
Commentary
Schattauer GmbH

Determination of the Putative Binding Sites for Thrombin Receptor Activating Peptide through a Hydropathic Complementary Approach

Jiří Suttnar
,
Jan E. Dyr
,
Lucie Dolečková
1   Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
› Author Affiliations
Further Information

Publication History

Received 18 June 1999

Accepted after resubmission 28 September 1999

Publication Date:
06 December 2017 (online)

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Summary

Putative binding sites in a platelet thrombin receptor (PAR-1) for the activating peptide SFLLRNPNDKYEPF (AP) and for the bradykinin analogue MKRPPGFSPFRSSRIG were revealed using a computer program for identifying complementary peptide segments. The program is based on the assumption that interactions of agonist’s peptides and protein’s receptors can be elucidated by complementary average hydropathies as much as possible equal by size and opposite by sign. Some of the computer-found putative binding sites were close to the supposed AP-PAR-1 contacts in the amino-terminal exodomain and in the second extracellulary loop of PAR-1. Peptides complementary to these binding sites were also computer-designed and were synthesized. They mostly inhibited the aggregation of gel filtered platelets by thrombin (0.025 U/mL) with IC50 in a high micromolar range of concentrations. The peptide complementary to site L258-Y269 of PAR-1 induced aggregation of gel filtered platelets with EC50 = 98 [µmol/L] related to thrombin (0.025 U/mL) aggregation response.

Keywords

Hydropathic complementarity - thrombin receptor
 

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