Development of a novel anti-platelet drug targeted for collagen-induced platelet aggregation

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AAPP, a mosquito saliva protein, specifically blocks platelet adhesion to collagen by binding directly to collagen and subsequently causing platelet aggregation. The aim of this study was to identify the active region of AAPP responsible for the anti-thrombotic activity because we hypothesized that AAPP could be used as a candidate anti-platelet drug. We identified that the essential moiety of AAPP for collagen binding and anti-thrombotic activity was in the region encoded by exon 3-4. The crystal structure of this domain was also determined. AAPP inhibited whole blood aggregation induced by collagen at 10 mg/kg body weight. AAPP prevented pulmonary death at a lower dose (3 mg/kg) without prolongation of bleeding time compared with aspirin (100 mg/kg) that compromised hemostasis. These results indicate that AAPP has great potential as a new anti-platelet agent with a better risk/benefit ratio than that seen with aspirin.