A mimetic of the RGDF-peptide [arginine-glycine-aspartic acid-phenylalanine] blocks aggregation and flow-induced platelet deposition on severely injured stenotic arterial wall. Effects on different animal models and in humans.
8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the tetrapeptide arginine-glycine-aspartic acid-phelylalanine, inhibits fibrinogen and vitronectin binding to GP IIb/IIIa. SC-49992 effects on impedance and optical aggregation were compared in different species (human, porcine and dog), SC-49992 induced significant inhibition both in whole blood and PRP aggregation, in all species; however, porcine platelets had a SC-49992 IC50 = 2.5 mM while human and dog platelets had a significant lower IC50 (1 microM and 1.5 microM, respectively). Inhibition of flow-mediated platelet deposition on severely injured vessels was studied in porcine blood at high and low shear rates for 5 minutes. Additionally, studies were performed in vessels with 80% stenosis. SC-49992 reduced platelet deposition both at high and low shear rate in parallel streamlined flow and in stenotic conditions. The lower affinity of porcine platelets for SC-49992 seems to be due to a species difference at the GPIIb/IIIa receptor RGD-sequence level.
Pueyo
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C
Cardiovascular Research Unit & Foundation, CSIC-HSCSP, Barcelona, Spain.
Badimon
J J
JJ
Royo
T
T
Feigen
L P
LP
Badimon
L
L
D000595:Amino Acid Sequence; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000293:injuries; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019030:Receptors, Vitronectin / Q000378:metabolism; D013552:Swine; D013927:Thrombosis / Q000097:blood; D019096:Vitronectin / Q000378:metabolism
C074050:8-guanidino-octanoyl-Asp-Phe; D004151:Dipeptides; D005353:Fibronectins; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D019096:Vitronectin; C084961:arginyl-glycyl-aspartyl-phenylalanine