Conformation of Peptide Model Molecules in Alcohol-Water Mixtures and Its Pressure Dependence

目前的研究主要集中在酒精诱导的蛋白质折叠，以阐明其在分子水平上的机制。首先，利用X射线和中子散射技术研究了在各种醇-水混合物中主要形成的溶剂团簇的结构和尺寸。研究表明，醇的疏水基团越大，在低醇浓度下，水的四面体结构越容易被破坏，导致醇分子容易聚集形成溶剂团簇。特别是，小角度中子散射实验的结果表明，三氟乙醇（TFE）和六氟异丙醇（HFIP）的氟代醇显着形成在其水溶液中的溶剂簇。这些发现以及氟代醇比脂肪醇（如乙醇（EtOH）和2-丙醇（2-PrOH））更强烈地诱导蛋白质折叠的事实表明簇形成与蛋白质折叠之间的关系。1，4-戊二醇分子的溶剂化行为，包括一个疏水的烃链和两个亲水的羟基，作为肽分子的模型，在不同的醇-水混合物中进行了研究。结果表明，在1，4-戊二醇水溶液中加入乙醇和2-丙醇可使1，4-戊二醇分子中的羟基脱水，而TFE和HFIP则与烃链发生强烈的相互作用。醇分子与1，4-戊二醇烃链间的疏水相互作用按HFIP>TFE>EtOH[约等于]2-PrOH的顺序较强。这一顺序与酒精对蛋白质折叠的影响一致。本研究表明，醇簇与蛋白质分子之间的相互作用对蛋白质折叠有重要贡献。

The present investigation has focused on alcohol-induced protein folding to clarify its mechanism at fee molecular level. Firstly, structure and size of solvent clusters predominantly formed in various alcohol-water mixtures have been investigated by using X-ray and neutron scattering techniques. It has been shown that the larger the hydrophobic group of alcohols, the more the tetrahedral-like structure of water is disrupted at low alcohol concentration, result in that alcohol molecules easily aggregate to form solvent clusters. In particular, the results from small-angel neutron scattering experiments have shown that fluoroalcohols of trifluoroethanol(TFE) and hexafluoroisopropanol(HFIP) significantly form solvent clusters in their aqueous solutions. These findings, together with the fact that the fluoroalcohols more strongly induce protein folding than aliphatic alcohols, such as ethanol(EtOH) and 2-propanol(2-PrOH), suggest the relation between cluster formation and protein folding.Solvation behavior of 1,4-pentanediol molecule, which involves a hydrophobic hydrocarbon chain and two hydrophilic hydroxyl groups, as a model of peptide molecule in various alcohol-water mixtures has been investigated by using infrared spectroscopy and NMR. The results have suggested that addition of ethanol and 2-propanol into aqueous 1,4-pentanediol solution induces to dehydration from the hydroxyl groups of 1,4-pentanediol molecule, whereas TFE and HFIP strongly interact to the hydrocarbon chain. It has also been shown that the hydrophobic interaction between alcohol molecule and the hydrocarbon chain of 1,4-pentanediol molecule is more stronger in the sequence of HFIP>TFE>EtOH【approximately equal】2-PrOH. This sequence is in agreement with that for the effect of alcohol on protein folding. The present investigation has suggested that interaction between alcohol clusters and protein molecule significantly contributes to protein folding.