Oligoarginine vectors for intracellular delivery: Role of arginine side-chain orientation in chain length-dependent destabilization of lipid membranes
Oligoarginine vectors for intracellular delivery: Role of arginine side-chain orientation in chain length-dependent destabilization of lipid membranes
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DOI：
10.1016/j.chemphyslip.2011.11.008
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发表时间：
2012-01-01
影响因子：
3.4
通讯作者：
Lensink, M. F.
中科院分区：
文献类型：
--
作者：
Bouchet, A. M.;Lairion, F.;Lensink, M. F.
富含精氨酸的肽由于其跨越不同类型的膜和在细胞内运输货物分子的能力而受到越来越多的关注。尽管肽诱导的去稳定化已被广泛研究，关于肽侧链和骨架相对于双层的取向知之甚少，这可能有助于肽诱导的膜扰动的分子理解。这项工作的主要目的是使用ATR-100提供精氨酸肽在PC和带负电荷的PG脂质体的脂质双层中的取向的详细描述。红外光谱和分子建模，并与这些取向的偏好，脂质双分子层disabilization.Molecular建模表明，以上的转变温度精氨酸侧链优先溶剂直接在PC/水界面，而几个精氨酸侧链指向PG的疏水核心。IR二色性光谱证实了精氨酸侧链垂直于脂质-水界面的取向。红外光谱显示一个随机分布的骨干，似乎是必不可少的优化与脂质膜的相互作用。所观察到的荧光染料渗透的增加与肽诱导的酰基链中的侧键的形成有关。在不存在疏水性残基的情况下，插入有利于磷酸盐/胍相互作用的侧链是膜透化的另一种机制，迄今为止尚未进一步分析。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Arginine-rich peptides receive increased attention due to their capacity to cross different types of membranes and to transport cargo molecules inside cells. Even though peptide-induced destabilization has been investigated extensively, little is known about the peptide side-chain and backbone orientation with respect to the bilayer that may contribute to a molecular understanding of the peptide-induced membrane perturbations.The main objective of this work is to provide a detailed description of the orientation of arginine peptides in the lipid bilayer of PC and negatively charged PG liposomes using ATR-IR spectroscopy and molecular modeling, and to relate these orientational preferences to lipid bilayer destabilization.Molecular modeling showed that above the transition temperature arginine side-chains are preferentially solvent-directed at the PC/water interface whereas several arginine side-chains are pointing towards the PG hydrophobic core. IR dichroic spectra confirmed the orientation of the arginine side chains perpendicular to the lipid-water interface. IR spectra shows an randomly distributed backbone that seems essential to optimize interactions with the lipid membrane. The observed increase of permeation to a fluorescent dye is related to the peptide induced-formation of gauche bonds in the acyl chains. In the absence of hydrophobic residues, insertion of side-chains that favors phosphate/guanidium interaction is another mechanism of membrane permeabilization that has not been further analyzed so far. (C) 2011 Elsevier Ireland Ltd. All rights reserved.