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Short-chain consensus alpha-neurotoxin: a synthetic 60-mer peptide with generic traits and enhanced immunogenic properties.
Amino Acids 2018; 50(7):885-895AA

Abstract

The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx. The synthetic ScNtx gene was de novo constructed and cloned into the expression vector pQE30 containing a 6His-Tag and an FXa proteolytic cleavage region. Escherichia coli Origami cells transfected with the pQE30/ScNtx vector expressed the recombinant consensus neurotoxin in a soluble form with a yield of 1.5 mg/L of culture medium. The 60-amino acid residue ScNtx contains canonical structural motifs similar to α-neurotoxins from African elapids and its LD50 of 3.8 µg/mice is similar to the most toxic short-chain α-neurotoxins reported from elapid venoms. Furthermore, ScNtx was also able to antagonize muscular, but not neuronal, nicotinic acetylcholine receptors (nAChR). Rabbits immunized with ScNtx were able to immune-recognize short-chain α-neurotoxins within whole elapid venoms. Type I neurotoxins are difficult to isolate and purify from natural sources; therefore, the heterologous expression of molecules such ScNtx, bearing crucial motifs and key amino acids, is a step forward to create common immunogens for developing cost-effective antivenoms with a wider spectrum of efficacy, quality and strong therapeutic value.

Authors+Show Affiliations

Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, UNAM, Apartado Postal 510-3, 61500, Cuernavaca, Morelos, Mexico.Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, UNAM, Apartado Postal 510-3, 61500, Cuernavaca, Morelos, Mexico. Departamento de Alimentos, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia, AA 1226, Medellín, Colombia.Instituto de Ciencias del Mar y Limnología/Posgrado en Ciencias del Mar y Limnologia, Universidad Nacional Autónoma de México, UNAM, Circuito exterior s/n, Ciudad Universitaria, 04510, Mexico City, Mexico.Instituto de Ciencias del Mar y Limnología/Posgrado en Ciencias del Mar y Limnologia, Universidad Nacional Autónoma de México, UNAM, Circuito exterior s/n, Ciudad Universitaria, 04510, Mexico City, Mexico.Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, UNAM, Apartado Postal 510-3, 61500, Cuernavaca, Morelos, Mexico. corzo@ibt.unam.mx. Institute of Biotechnology-UNAM, Av. Universidad 2001, 62210, Cuernavaca, Morelos, Mexico. corzo@ibt.unam.mx.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29626299

Citation

de la Rosa, Guillermo, et al. "Short-chain Consensus Alpha-neurotoxin: a Synthetic 60-mer Peptide With Generic Traits and Enhanced Immunogenic Properties." Amino Acids, vol. 50, no. 7, 2018, pp. 885-895.
de la Rosa G, Corrales-García LL, Rodriguez-Ruiz X, et al. Short-chain consensus alpha-neurotoxin: a synthetic 60-mer peptide with generic traits and enhanced immunogenic properties. Amino Acids. 2018;50(7):885-895.
de la Rosa, G., Corrales-García, L. L., Rodriguez-Ruiz, X., López-Vera, E., & Corzo, G. (2018). Short-chain consensus alpha-neurotoxin: a synthetic 60-mer peptide with generic traits and enhanced immunogenic properties. Amino Acids, 50(7), pp. 885-895. doi:10.1007/s00726-018-2556-0.
de la Rosa G, et al. Short-chain Consensus Alpha-neurotoxin: a Synthetic 60-mer Peptide With Generic Traits and Enhanced Immunogenic Properties. Amino Acids. 2018;50(7):885-895. PubMed PMID: 29626299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Short-chain consensus alpha-neurotoxin: a synthetic 60-mer peptide with generic traits and enhanced immunogenic properties. AU - de la Rosa,Guillermo, AU - Corrales-García,Ligia L, AU - Rodriguez-Ruiz,Ximena, AU - López-Vera,Estuardo, AU - Corzo,Gerardo, Y1 - 2018/04/06/ PY - 2018/01/29/received PY - 2018/03/13/accepted PY - 2018/4/8/pubmed PY - 2019/1/31/medline PY - 2018/4/8/entrez KW - Antisera KW - Elapid KW - Micrurus KW - Recombinant KW - Synthetic gene KW - Three finger toxins KW - α-Neurotoxin SP - 885 EP - 895 JF - Amino acids JO - Amino Acids VL - 50 IS - 7 N2 - The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx. The synthetic ScNtx gene was de novo constructed and cloned into the expression vector pQE30 containing a 6His-Tag and an FXa proteolytic cleavage region. Escherichia coli Origami cells transfected with the pQE30/ScNtx vector expressed the recombinant consensus neurotoxin in a soluble form with a yield of 1.5 mg/L of culture medium. The 60-amino acid residue ScNtx contains canonical structural motifs similar to α-neurotoxins from African elapids and its LD50 of 3.8 µg/mice is similar to the most toxic short-chain α-neurotoxins reported from elapid venoms. Furthermore, ScNtx was also able to antagonize muscular, but not neuronal, nicotinic acetylcholine receptors (nAChR). Rabbits immunized with ScNtx were able to immune-recognize short-chain α-neurotoxins within whole elapid venoms. Type I neurotoxins are difficult to isolate and purify from natural sources; therefore, the heterologous expression of molecules such ScNtx, bearing crucial motifs and key amino acids, is a step forward to create common immunogens for developing cost-effective antivenoms with a wider spectrum of efficacy, quality and strong therapeutic value. SN - 1438-2199 UR - https://www.unboundmedicine.com/medline/citation/29626299/Short-chain_consensus_alpha-neurotoxin:_a_synthetic_60-mer_peptide_with_generic_traits_and_enhanced_immunogenic_properties L2 - https://dx.doi.org/10.1007/s00726-018-2556-0 DB - PRIME DP - Unbound Medicine ER -