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 p,M and 104.50 p[M, 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. (c) 2013 Elsevier Inc. All rights reserved.