A novel peptide inhibitor of platelet aggregation from stiff silkworm, Bombyx batryticatus.

A novel platelet aggregation inhibitory peptide, named BB octapeptide, was isolated from stiff silkworm (Bombyx batryticatus) by gel filtration, anion-exchange, and reverse-phase high performance liquid chromatography. The molecular mass of the peptide was determined to be 885 Da using electrospray ionization mass spectrometry, and the sequence was identified as Asp-Pro-Asp-Ala-Asp-IIe-Leu-Gln using the Edman degradation method. To test its biological activity, the peptide was chemically synthesized using Fmoc solid-phase synthesis method. BB octapeptide inhibited rabbit platelet aggregation that was induced by collagen and epinephrine, with the IC50 values of 91.14 μM and 104.50 μM, respectively. After intravenous administrated in mice (30 mg/kg, 4 days), BB octapeptide showed similar ex vivo efficacy of inhibiting platelet aggregation as aspirin (10 mg/kg). In addition, this peptide prevented paralysis and death in pulmonary thromboembolism model and significantly reduced ferric chloride-induced thrombus formation in rats. Moreover, it exhibited low cytotoxicity in a cellular model. In conclusion, this is the first report that a novel platelet aggregation inhibitory peptide was isolated from stiff silkworm (B. batryticatus). Due to the excellent efficacy in reducing platelet aggregation and low toxicity, it can be a valuable lead compound for new drug design and development.