Abstract:Platelet integrin αlIbβ3 plays a critical role in both hemostasis and thrombosis. Current αIIbβ3 antagonists are potent anti-thrombotic drugs, but also cause adverse outcomes, which limited their clinical use. Drug-induced serious bleeding, thrombocytopenia and paradoxical thrombosis have been linked to impaired clot retraction and to conformational changes in αIIbβ3 that promote binding of preformed antibodies, natural ligands or both to αIIbβ3. We have used structure-guided design to generate the orthosteric… Show more
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