title: A novel peptide inhibitor of platelet aggregation from stiff silkworm, Bombyx batryticatus.
abstract: 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.
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: yikong668@sohu.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Kong
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Zhi-Long
authors.initials: ZL
authors.lastname: He
authors.affiliation: School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Qiu-Mei
authors.initials: QM
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Jin-Bin
authors.initials: JB
authors.lastname: Wang
authors.affiliation: School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: xming@email.unc.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Ming
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
chemical_list: D010975:Platelet Aggregation Inhibitors
keywords: BB octapeptide; Bleeding time; Bombyx batryticatus; Ferric chloride-induced thrombosis; Platelet aggregation; Pulmonary thromboembolism