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Amino Acids

, Volume 13, Issue 2, pp 171–181 | Cite as

Synthesis of salicyl-peptides and their effect on human platelet aggregationin vitro

  • G. Stavropoulos
  • V. Magafa
  • M. Liakopoulou-Kyriakides
  • Z. Sinakos
  • A. Aaberg
Full Papers

Summary

A series of leucine dipeptide amides containing at their N-terminal amino group the salicyl-residue [(o)-RO-C6H4-CO-, where R=H or CH3CO] have been synthesized by conventional solution techniques and tested for their inhibitory activity on human platelet aggregationin vitro induced by collagen, ADP or adrenaline. The salicyl-peptide (o)-HO-C6H4-CO-Leu-Asp(OBzl)-NH2 was found to exert strong inhibitory activity on platelet aggregation induced by collagen with an IC50 value 4.5 mM. The corresponding dipetide H2N-Leu-Asp(OVzl)-NH2 was also examined and was found to be less active, indicating that the presence of the lipophilicβ-benzyl ester group in combination with the salicyl group enhance the inhibitory activity. All the other salicyl-peptides examined either didn't show any inhibitory or aggregatory activity or a slight inhibition at the concentration of 9–10 mm.

Keywords

Amino acids Collagen Inhibitory activity Platelet aggregation Salicyl-peptides 

Abbreviations

The abbreviations used are in accordance with the rules of IUPAC-IUB Joint Commission on Biochemical Nomenclature: Eur J Biochem (1984) 138: 9–37; J Biol Chem (1989) 264: 663–673. Additional abbreviations are:

ADP

adenosine diphosphate

Boc

tert-butyloxycarbonyl

Bzl

benzyl

DIEA

N,N-diisopropylethylamine

DMSO

dimethyl sulfoxide

DMF

N,N-dimethylformamide

EtOAc

ethyl acetate

FCC

flash column chromatography

IC50

molar concentration of salicyl-peptide for 50% inhibition of platelet aggregation

iso-BCF

isobutyl chloroformate

NMM

N-methylmorpholine

PyBOP

(benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate

TLC

thin layer chromatography

TMS

tetramethylsilane

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Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • G. Stavropoulos
    • 1
  • V. Magafa
    • 1
  • M. Liakopoulou-Kyriakides
    • 2
  • Z. Sinakos
    • 3
  • A. Aaberg
    • 4
  1. 1.Department of ChemistryUniversity of PatrasPatrasGreece
  2. 2.Department of Chemical EngineeringUniversity of ThessalonikiGreece
  3. 3.Section of Hematology, Department of MedicineUniversity of ThessalonikiGreece
  4. 4.Department of ChemistryUniversity of BergenNorway

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