Jennings L K, White M M
Department of Medicine, University of Tennessee, Memphis, USA.
Am Heart J. 1998 May;135(5 Pt 2 Su):S179-83. doi: 10.1016/s0002-8703(98)70246-7.
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.
糖蛋白（GP）IIb/IIIa是急性冠状动脉综合征期间阻断血小板聚集的治疗靶点。人们制备了肽、肽模拟物和抗体，它们可竞争性阻断纤维蛋白原或血管性血友病因子与活化的GPIIb/IIIa复合物的结合。这些受体阻滞剂与GPIIb/IIIa的结合有效抑制了血小板聚集体的形成，因为配体与活化的GPIIb/IIIa的结合是血栓形成的最终共同途径。此外，结合的拮抗剂会诱导受体发生构象变化。这种构象变化，也称为配体诱导结合位点，可用作GPIIb/IIIa受体阻滞剂占据受体的标志物。利用与拮抗剂结合的GPIIb/IIIa具有高亲和力的D3单克隆抗体的结合特性，我们开发了一种监测GPIIb/IIIa拮抗剂受体阻断程度的新方法。该方法相对于聚集试验的患者间变异性具有特定优势，并为评估GPIIb/IIIa阻断的适当目标水平提供了一种方法。
