1. Expression of ligand-induced binding sites on glycoprotein IIb/IIIa complexes and the effect of various inhibitors
- Author
-
Jennings, Lisa K. and White, Melanie M.
- Subjects
Von Willebrand factor -- Chemical properties ,Monoclonal antibodies -- Chemical properties ,Fibrin -- Chemical properties ,Peptides -- Chemical properties ,Blockades -- Chemical properties ,Fibrinogen -- Chemical properties ,Health - Abstract
Byline: Lisa K. Jennings, Melanie M. White Abstract: Glycoprotein (GP) IIb/IIIa is a therapeutic target for the blockade of platelet aggregation during acute coronary syndromes. Peptides, peptidomimetics, and antibodies are generated that competitively block the binding of fibrinogen or von Willebrand factor to the activated GPIIb/IIIa complex. Binding of these receptor blockades to GPIIb/IIIa effectively inhibits the formation of the platelet aggregate because ligand binding to the activated GPIIb/IIIa is the final common pathway to thrombus formation. In addition, bound antagonists induce a conformational change in the receptor. This conformational change, also called a ligand-induced binding site, can be used as a marker for receptor occupancy by GPIIb/IIIa receptor blockades. Using the binding properties of the D3 monoclonal antibody that binds with high affinity to the antagonist bound GPIIb/IIIa, we have developed a new method for monitoring the extent of receptor blockade by GPIIb/IIIa antagonists. This method has specific advantages over the interpatient variability of the aggregation assay and provides a method for the evaluation of appropriate target levels of GPIIb/IIIa blockade. (Am Heart J 1998;135:S179-S183.) Author Affiliation: Memphis, Tenn Article Note: (footnote) [star] From the Departments of aMedicine and bBiochemistry, University of Tennessee., [star][star] Reprint requests: Dr. Lisa K. Jennings, Department of Medicine, 956 Court Ave., Coleman Building, Room H335, Memphis, TN 38163. E-mail: ljennings@utmem1.utmem.edu, a 4/0/87666
- Published
- 1998