Anti-platelet activity of the peptides composing the lebetin 1 family, a new class of inhibitors of platelet aggregation.

Abstract : We have purified from Vipera lebetina venom a family of inhibitors of platelet aggregation, named Lebetins. They are composed of two peptide groups of short (Lebetin 1: L1alpha: GDNKPPKKGPPNG; L1beta: DNKPPKKGPPNG) and long (Lebetin 2: L2alpha: GDNKPPKKGPPNGCFGHKIDRIGSHSGLGCNKVDDNKG; L2beta: DNKPPKKGPPNGCFGHKIDRIGSHSGLGCNKVDDNKG) size. The sequence presenting anti-platelet activity is mainly present within the Lebetin 1 sequence [Barbouche, R. Marrakchi, N., Mansuelle, P., Krifi, M., Fenouillet, E., Rochat, H. and El Ayeb, M. (1996) Novel anti-platelet aggregation polypeptides from Vipera lebetina venom: isolation and characterization. FEBS Lett. 392, 6-10]. Here, the peptides that compose the Lebetin 1 family were synthesized. Their respective activity was determined. Synthetic L1alpha and L1beta inhibited collagen-induced platelet aggregation in the nanomolar range. A peptide corresponding to L1beta deleted by D at its N terminus (L1gamma) also inhibited platelet aggregation potently; further truncation of L1gamma impaired its activity. Because L1 peptides efficiently inhibited fibrinogen-induced alpha-chymotrypsin treated-platelet aggregation, we tested whether they act mainly through the inhibition of platelet binding to fibrinogen and showed that they failed to inhibit platelet binding to fibrinogen-coated wells. The activity of L1 peptides was also tested in vivo: their intravenous administration strongly inhibited collagen-induced thrombocytopenia in rats.
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Submitted on : Friday, January 18, 2019 - 11:22:25 AM
Last modification on : Wednesday, July 17, 2019 - 1:32:31 AM

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R. Barbouche, M. Marrakchi, M. Mabrouk, Mohamed Naceur Krifi, J van Rietschoten, et al.. Anti-platelet activity of the peptides composing the lebetin 1 family, a new class of inhibitors of platelet aggregation.. Toxicon, Elsevier, 1998, 36 (12), pp.1939-1947. ⟨10.1016/S0041-0101(98)00118-4⟩. ⟨pasteur-01985732⟩

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