Tsikaris Vassilios
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45 110 Ioannina, Greece.
J Pept Sci. 2004 Oct;10(10):589-602. doi: 10.1002/psc.603.
Activation of the platelet surface receptor GPIIb/IIIa is the final pathway of platelet aggregation, regardless of the initiating stimulus. RGD analogues, peptidomimetics and monoclonal antibodies to GPIIb/IIIa have been developed targeting the blockage of the receptor and inhibition of the fibrinogen binding. However, the intrinsic activating effect of GPIIb/IIIa blockers is widely discussed as one potential contributing factor for the disappointing outcome of trials with GPIIb/IIIa inhibitors. An alternative method for thrombus prevention could be the use of specific fibrinogen blockers since they will act at the final step of the platelet aggregation and are expected to leave the receptor unaffected. To achieve this target the design of the fibrinogen ligands could be based on (i) sequences derived from GPIIb/IIIa ligand binding sites, and (ii) sequences complementary to RGD and/or to fibrinogen gamma-chain. The available information, which could be used as a starting point for developing potent fibrinogen ligands, is reviewed.
血小板表面受体糖蛋白IIb/IIIa的激活是血小板聚集的最终途径，无论起始刺激因素如何。已开发出RGD类似物、拟肽和针对糖蛋白IIb/IIIa的单克隆抗体，旨在阻断该受体并抑制纤维蛋白原结合。然而，糖蛋白IIb/IIIa阻滞剂的内在激活作用作为导致糖蛋白IIb/IIIa抑制剂试验结果令人失望的一个潜在因素受到广泛讨论。预防血栓的另一种方法可能是使用特异性纤维蛋白原阻滞剂，因为它们将作用于血小板聚集的最后一步，并且预计不会影响受体。为实现这一目标，纤维蛋白原配体的设计可基于：（i）源自糖蛋白IIb/IIIa配体结合位点的序列，以及（ii）与RGD和/或纤维蛋白原γ链互补的序列。本文综述了可作为开发强效纤维蛋白原配体起点的现有信息。
