Open AccessLebetin Peptides: Potent Platelet Aggregation Inhibitors
Author(s) -
Naziha Marrakchi,
Kamel Mabrouk,
Imed Regaya,
Sameh Sarray,
Mohamed Fathallah,
Hervé Rochat,
M. El Ayeb
Publication year - 2001
Publication title -
pathophysiology of haemostasis and thrombosis
Language(s) - Uncategorized
Resource type - Journals
eISSN - 1424-8840
pISSN - 1424-8832
DOI - 10.1159/000048064
Subject(s) - chemistry , peptide , platelet , in vitro , platelet aggregation , venom , thrombin , biochemistry , ic50 , platelet activation , platelet aggregation inhibitor , biology , immunology , aspirin
Lebetins from Macrovipera lebetina snake venom constitute a new class of inhibitors of platelet aggregation. There are two groups of peptides: lebetin 1 (L1; 11- to 13-mer) and lebetin 2 (L2; 37- to 38-mer). The short lebetins are identical to the N-terminal segments of the longer ones. They inhibit platelet aggregation induced by various agonists (e.g. thrombin, PAF-acether or collagen). The shortest lebetin (11-mer) shows potent inhibition of rabbit (IC(50) = 7 nM) and human (IC(50) = 5 nM) platelets. They prevent collagen-induced thrombocytopenia in rats. N- and C-terminal-truncated synthetic L1gamma (sL1gamma; 11-mer) is less active in inhibiting platelet aggregation than the native peptide. Results from Ala scan studies of the sL1gamma peptide indicated that replacement of the residues (P3, G7, P8, P9 or N10) resulted in a remarkable drop in the activity, whereas replacement of residues K2, P4 or K6 by Ala resulted in enhancement of the antiplatelet activity by at least 10-fold. To examine the activity of multimeric L1gamma, several multimeric peptides were synthesized using the multiple-antigen peptide system assembled on a branched lysine core and their antiplatelet activity was evaluated in vitro. The largest multimeric peptides showed a 1,000-fold increase in antiplatelet activity.