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上，以期在分子水平上阐明其作用机制。首先，用X射线和中子散射技术研究了在不同的醇-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，水的类四面体结构在低浓度时就越容易被破坏，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)的氟醇在其水溶液中显著地形成了溶剂簇合物。这些发现，再加上氟醇比脂肪醇(如乙醇和异丙醇)更强地诱导蛋白质折叠，暗示了蛋白质折叠与簇形成的关系。用红外光谱和核磁共振研究了1，4-戊二醇分子在不同醇-水混合物中的溶剂化行为。1，4-戊二醇分子包括一个疏水碳链和两个亲水羟基。结果表明，在1，4-戊二醇水溶液中加入乙醇和异丙醇会导致1，4-戊二醇分子中羟基的脱水，而TFE和HFIP则与碳氢链发生强烈的相互作用。结果还表明，醇分子与1，4-戊二醇分子碳链之间的疏水相互作用较强，顺序为HFIP&GT；TFE&GT；Etoh[大致相等]2-Proh。这个序列与酒精对蛋白质折叠影响的序列是一致的。目前的研究表明，醇团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.