Inhibition of platelet-vessel wall interaction. Platelet receptors, monoclonal antibodies, and synthetic peptides.
Platelet adhesion to blood vessel walls and subsequent aggregation require binding of von Willebrand factor to glycoprotein receptors on the platelet cell membrane. Consequently, inhibition of binding to these glycoproteins by monoclonal antibodies or synthetic peptides could provide a useful approach to the treatment of thrombotic conditions. Most of the studies that have used this approach have focused on glycoprotein IIb/IIIa, which is a multispecific receptor that binds von Willebrand factor, fibrinogen, fibronectin, and vitronectin, all of which are involved in cell adhesion. In animal studies, monoclonal antibodies raised against glycoprotein IIb/IIIa cause an increase in bleeding time, indicative of impaired platelet function, and there is some evidence that these antibodies are more effective at reducing platelet adhesion than anticoagulants or thromboxane synthase inhibitors. Furthermore, as glycoprotein IIb/IIIa binds several proteins involved in cell adhesion, many of which bear the amino acid sequence Arg-Gly-Asp, it may be possible to prevent thrombus formation by the use of synthetic peptides containing this sequence.
Ruggeri
Z M
ZM
Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006801:Humans; D008969:Molecular Sequence Data; D010973:Platelet Adhesiveness; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D014841:von Willebrand Factor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor