A novel human recombinant antibody fragment capable of neutralizing Mexican scorpion toxins
Por:
Riano-Umbarila, L, Olamendi-Portugal, T, Morelos-Juarez, C, Gurrola, GB, Possani, LD, Becerril, B
Publicada:
15 dic 2013
Categoría:
Toxicology
Resumen:
Using phage display and directed evolution, our group has progressed in the construction of a second family of human single chain variable fragments (scFv) which bind to scorpion toxins dangerous to mammals. It was observed that scFv C1 only bound initially to toxin Cn2, which constitutes 6.8% of whole venom from the scorpion Centruroides noxius Hoffman. Only a few amino acid changes were necessary to extend its recognition to other similar toxins and without affecting the recognition for its primary antigen (Cn2 toxin). One variant of scFv C1 (scFv 202F) was selected after two cycles of directed evolution against Cll1 toxin, the second major toxic component from the venom of the Mexican scorpion Centruroides limpidus limpidus Karsh (0.5% of the whole venom). scFv 202F is also capable of recognizing Cn2 toxin. Despite not having the highest affinity for toxins Cll1 (KD = 25.1 × 10-9 M) or Cn2 (KD = 8.1 × 10-9 M), this antibody fragment neutralized one LD50 of each one of these toxins. Additionally, scFv 202F moderately recognized Cll2 toxin which constitutes 1.5% of the venom from C. limpidus. Based on our previous experience, we consider that these results are promising; consequently, we continue working on generating new optimized variants from scFv C1 that could be part of a recombinant scorpion anti-venom from human origin, that might reach the market in the near future. © 2013 Elsevier Ltd. All rights reserved.
Filiaciones:
Riano-Umbarila, L:
UNAM, Inst Biotecnol, Dept Med Mol & Bioproc, Cuernavaca 62250, Morelos, Mexico
Olamendi-Portugal, T:
UNAM, Inst Biotecnol, Dept Med Mol & Bioproc, Cuernavaca 62250, Morelos, Mexico
Morelos-Juarez, C:
UNAM, Inst Biotecnol, Dept Med Mol & Bioproc, Cuernavaca 62250, Morelos, Mexico
Gurrola, GB:
UNAM, Inst Biotecnol, Dept Med Mol & Bioproc, Cuernavaca 62250, Morelos, Mexico
Possani, LD:
UNAM, Inst Biotecnol, Dept Med Mol & Bioproc, Cuernavaca 62250, Morelos, Mexico
Becerril, B:
UNAM, Inst Biotecnol, Dept Med Mol & Bioproc, Cuernavaca 62250, Morelos, Mexico
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