Anti-platelet activity of the peptides composing the lebetin 1 family, a new class of inhibitors of platelet aggregation.
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.
Barbouche
R
R
Laboratoire Venins et Toxines, Institut Pasteur de Tunis, Tunisia.
Marrakchi
N
N
Mabrouk
K
K
Krifi
M N
MN
Van Rietschoten
J
J
Fenouillet
E
E
El Ayeb
M
M
Rochat
H
H
D000595:Amino Acid Sequence; D000818:Animals; D003094:Collagen / Q000009:adverse effects; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology* / Q000633:toxicity; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013921:Thrombocytopenia / Q000139:chemically induced; D014757:Viper Venoms / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D014757:Viper Venoms; C101100:lebetin 1; D003094:Collagen