Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/60367
Type: Artigo de periódico
Title: Interaction of local anesthetics with a peptide encompassing the IV/S4-S5 linker of the Na+ channel
Author: Fraceto, LF
Oyama, S
Nakaie, CR
Spisni, A
de Paula, E
Pertinhez, TA
Abstract: The peptide pIV/S4-S5 encompasses the cytoplasmic linker between helices S4-S5 in domain IV of the voltage-gated Na+ channel, residues 1644-1664. (2)The interaction of two local anesthetics (LA), lidocaine and benzocaine, with pIV/S4-S5 has been studied by DOSY, heteronuclear NMR H-1-N-15-HSQC spectroscopy and computational methods. DOSY indicates that. benzocaine, a neutral ester, exhibits stronger interaction with pIV/S4-S5 than lidocaine, a charged amine-amide. Weighted average chemical shifts, Delta delta(H-1-N-15), show that benzocaine affects residues L-1653, M-1655 and S-1656 while lidocame slightly perturbs residues I-1646, L-1649 and A(1659), L-1660, near the N-and C-terminus, respectively. Computational methods confirmed the stability of the benzocaine binding and the existence of two binding sites for lidocaine. Even considering that the approach of studying the peptide in the presence of a co-solvent (TFE/H2O, 30%/70% v/v) has an inherently limited implication, our data strongly support the existence of multiple LA binding sites in the IV/S4-S5 linker, as suggested in the literature. In addition, we consider that LA can bind to the S4-S5 linker with diverse binding modes and strength since this linker is part of the receptor for the "inactivation gate particle". Conditions for devising new functional studies, aiming to better understand Na+ channel functionality as well as the various facets of LA pharmacological activity are proposed in this work. (c) 2006 Elsevier B.V. All rights reserved.
Subject: voltage-gated sodium channel
peptide
local anesthetics
benzocaine
lidocame
nuclear magnetic resonance
Country: Holanda
Editor: Elsevier Science Bv
Rights: fechado
Identifier DOI: 10.1016/j.bpc.2006.03.010
Date Issue: 2006
Appears in Collections:Unicamp - Artigos e Outros Documentos

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