Neutralizing interaction between heparins and myotoxin II, a lysine 49 phospholipase A2 from Bothrops asper snake venom. Identification of a heparin-binding and cytolytic toxin region by the use of synthetic peptides and molecular modeling.

Heparin binds to phospholipase 4 myotoxins fromBothrops asper snake venom, inhibiting their toxic activities.This interaction was investigated using purified myotoxin 11, a Lys-49 phospholipase A, of this venom, and a series of heparin variants, fragments, and other glycosaminoglycans.The binding was correlated to toxin neutralization, using endothelial cells as a target.Myotoxin I1 binds radiolabeled heparin in solution unselectively, and forms macromolecular complexes with an optimum at a heparin:toxin molar ratio of 1:5.Both O-sulfates and N-sulfates play a role in heparin binding, in the order of importance 2-O-sulfates > 6-Osulfates > N-sulfates.The shortest heparin oligosaccharides interacting with myotoxin I1 are hexasaccharides.The binding of a neutralizing monoclonal antibody (MAb-3) to myotoxin I1 was not inhibited by heparin, indicating that the two molecules interact with different sites on the toxin.A synthetic peptide (residues 115-129 in the numbering system of Renetseder et al. (Renetseder, R.,

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