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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Interaction of local anesthetics with a peptide encompassing the IV/S4-S5 linker of the Na+ channel
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Interaction of local anesthetics with a peptide encompassing the IV/S4-S5 linker of the Na+ channel

机译：局部麻醉药与包含Na +通道IV / S4-S5接头的肽的相互作用

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摘要

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.
机译：肽pIV / S4-S5包含电压门控Na +通道结构域IV（残基1644-1664）中螺旋S4-S5之间的胞质接头。 （2）通过DOSY，异核NMR H-1-N-15-HSQC光谱和计算方法研究了利多卡因和苯佐卡因这两种局麻药与pIV / S4-S5的相互作用。 DOSY表示这一点。中性酯苯佐卡因与带电荷的胺基酰胺利多卡因相比，与pIV / S4-S5的相互作用更强。加权平均化学位移Delta delta（H-1-N-15）表明，苯佐卡因会影响残基L-1653，M-1655和S-1656，而利多卡因会轻微干扰残基I-1646，L-1649和A（1659） ，L-1660，分别位于N端和C端附近。计算方法证实了苯佐卡因结合的稳定性以及利多卡因的两个结合位点的存在。即使考虑到在共溶剂（TFE / H2O，30％/ 70％v / v）存在下研究多肽的方法固有地有限的含义，我们的数据也强烈支持在多肽中存在多个LA结合位点。如文献中所建议的，IV / S4-S5接头。另外，我们认为LA可以以不同的结合方式和强度结合到S4-S5接头上，因为该接头是“灭活门颗粒”受体的一部分。在这项工作中提出了设计新功能研究的条件，旨在更好地理解Na +通道功能以及LA药理活性的各个方面。 （c）2006 Elsevier B.V.保留所有权利。

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