Synthesis of salicyl-peptides and their effect on human platelet aggregationin vitro |
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Authors: | Dr G Stavropoulos V Magafa M Liakopoulou-Kyriakides Z Sinakos A Aaberg |
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Institution: | (1) Department of Chemistry, University of Patras, GR-26500 Patras, Greece;(2) Department of Chemical Engineering, University of Thessaloniki, Greece;(3) Section of Hematology, Department of Medicine, University of Thessaloniki, Greece;(4) Department of Chemistry, University of Bergen, Norway |
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Abstract: | 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 lipophilic-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.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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Keywords: | Amino acids Collagen Inhibitory activity Platelet aggregation Salicyl-peptides |
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