Synthetic RGD peptides derived from the adhesive domains of snake-venom proteins: evaluation as inhibitors of platelet aggregation.
Synthetic peptides based on the RGD domains of the potent platelet aggregation inhibitors kistrin and dendroaspin were generated. The 13-amino-acid peptides were synthesized as dicysteinyl linear and disulphide cyclic forms. In platelet-aggregation studies, the cyclic peptides showed 3-fold better inhibition than their linear equivalents and approx. 100-fold greater potency than synthetic linear RGDS peptides derived from fibronectin. An amino acid substitution, Asp10-->Ala, in the kistrin-based peptide gave a 4-fold decrease in potency in the linear peptide, but produced a 2-fold elevation in the inhibitory activity of the cyclic form, generating a peptide of potency comparable with that of the parent protein.
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Protein Biochemistry Section, Thrombosis Research Institute, London, U.K.
Deadman
J J
JJ
Williams
J A
JA
Kakkar
V V
VV
Rahman
S
S
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D004546:Elapid Venoms / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000302:isolation & purification / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D012910:Snake Venoms / Q000302:isolation & purification / Q000494:pharmacology*
D004546:Elapid Venoms; D009498:Neurotoxins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D012910:Snake Venoms; C064594:elegantin; C064595:albolabrin; C074772:mambin; D000244:Adenosine Diphosphate; C047981:arginyl-glycyl-aspartic acid; C067623:kistrin