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

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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.

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Abbreviations

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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Stavropoulos, G., Magafa, V., Liakopoulou-Kyriakides, M. et al. Synthesis of salicyl-peptides and their effect on human platelet aggregationin vitro . Amino Acids 13, 171–181 (1997). https://doi.org/10.1007/BF01373215

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  • DOI: https://doi.org/10.1007/BF01373215

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