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Publicaciones en VIVO

Lintner, B. R.

Artículo académico Persona
Rutgers University, New Brunswick, NJ, United States

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  • Phospholipases A2 (PLA2) with skeletal muscle-damaging activity are widely distributed among venomous snakes. In the genus Bothrops, there is a family of basic myotoxins sharing a high structural homology, antigenic cross-reactivity and pharmacological properties. Its members seem to fall into two categories: enzymatically-active (Asp-49) PLA2s and enzymatically-inactive (Lys-49) PLA2-like proteins. B. asper myotoxin II and B. jararacussu myotoxin I are two well-characterized proteins of the latter group, which demonstrates that PLA2 activity is not required for the expression of their muscle-damaging activity. B. asper myotoxin II, in addition, is capable of inducing edema and of lysing a variety of cultured cell types.

    Neutralization of B. asper myotoxin II has been studied using polyclonal and monoclonal antibodies as well as heparins. Using synthetic peptides of myotoxin II, a heparin-binding region has been identified. The interaction of heparins with this site, including residues 115-129 (with a possible contribution of residues 36 and 38) leads to the neutralization of its myotoxic and cytolytic activities. In contrast to two other peptides of myotoxin II, peptide 115-129 is capable of lysing endothelial cells, albeit with ~10-fold lower efficiency than the toxin. However, no evidence of myonecrosis has been obtained upon injection of this peptide. Molecular dynamics analyses predict that the three-dimensional structure of the free peptide may be similar to its native conformation, according to the crystal structure of myotoxin II. By coupling peptide 115-129 to diphtheria toxoid as a carrier, rabbit antibodies have been raised. These antibodies recognize both the peptide and the toxin, in agreement with this prediction. The neutralizing ability of these site-specific antibodies is currently being investigated.

fecha de publicación

  • 1997