Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Characterization of selectivity and pharmacophores of type 1 sea anemone toxins by screening seven Na-v sodium channel isoforms

Texto completo
Autor(es):
Zaharenko, Andre Junqueira [1] ; Schiavon, Emanuele [2] ; Ferreira, Jr., Wilson Alves [3] ; Lecchi, Marzia [2] ; de Freitas, Jose Carlos [3] ; Richardson, Michael [4] ; Wanke, Enzo [2]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] IPEN, Ctr Biotecnol, BR-05508000 Sao Paulo - Brazil
[2] Univ Milano Bicocca, Dipartimento Biotecnol & Biosci, I-20126 Milan - Italy
[3] Univ Sao Paulo, Dept Fisiol, Inst Biociencias, BR-05508900 Sao Paulo - Brazil
[4] Fundacao Ezequiel Dias FUNED, BR-30510010 Belo Horizonte, MG - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Peptides; v. 34, n. 1, SI, p. 158-167, MAR 2012.
Citações Web of Science: 7
Resumo

During their evolution, animals have developed a set of cysteine-rich peptides capable of binding various extracellular sites of voltage-gated sodium channels (VGSC). Sea anemone toxins that target VGSCs delay their inactivation process, but little is known about their selectivities. Here we report the investigation of three native type 1 toxins (CGTX-II, delta-AITX-Bcg1a and delta-AITX-Bcg1b) purified from the venom of Bunodosoma cangicum. Both delta-AITX-Bcg1a and delta-AITX-Bcg1b toxins were fully sequenced. The three peptides were evaluated by patch-clamp technique among Nav1.1-1.7 isoforms expressed in mammalian cell lines, and their preferential targets are Na(v)1.5 > 1.6 > 1.1. We also evaluated the role of some supposedly critical residues in the toxins which would interact with the channels, and observed that some substitutions are not critical as expected. In addition, CGTX-II and delta-AITX-Bcg1a evoke different shifts in activation/inactivation Boltzmann curves in Nav1.1 and 1.6. Moreover, our results suggest that the interaction region between toxins and VGSCs is not restricted to the supposed site 3 (S3-54 linker of domain IV), and this may be a consequence of distinct surface of contact of each peptide vs. targeted channel. Our data suggest that the contact surfaces of each peptide may be related to their surface charges, as CGTX-II is more positive than delta-AITX-Bcg1a and delta-AITX-Bcg1b. (C) 2011 Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 07/56525-3 - Construção de uma biblioteca de cDNA dos tentáculos da anêmona do mar Bunodosoma cangicum e clonagem de neurotoxinas
Beneficiário:Andre Junqueira Zaharenko
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 06/02892-2 - Caracterização do efeito analgésico do composto LAS 390 obtido da peçonha da anêmona Bunodosoma cangicum
Beneficiário:Wilson Alves Ferreira Júnior
Linha de fomento: Bolsas no Brasil - Iniciação Científica