Study on the molecular conformational equilibrium of butane for the development of an experimental model system of the hydrophobic effect

众所周知，疏水效应是蛋白质结构稳定性的关键因素。本计画的目的是发展一个疏水效应的实验模型。作为模型，我们用拉曼光谱研究了简单链状分子的构象平衡。最简单、最理想的模型是丁烷的反偏平衡。我们首先在水溶液中靶向该系统。然而，由于丁烷在水中的低溶解度，很难通过拉曼光谱观察到平衡。在本项目期间，我们成功地观察到定性的平衡，表明相对于有机溶剂系统的gauche构象的相对人口增加。定量分析的进一步实验正在进行中。作为另一个目标，我们研究了二乙基二硫化物的trans-gauche/gauche-gauche平衡，这是蛋白质二硫键的模型。阐明了温度和压力对平衡的影响，并与蛋白质二硫键展开时的构象变化进行了比较。其他研究结果是在简单肽体系中获得的。我们的目标是一个简单的富含丙氨酸的肽作为模型分子，这是适合于观察在水中的螺旋-卷曲平衡。压力对平衡的影响表明，螺旋形式的相对群体随着压力的增加而增加。这种行为显然与压力诱导的蛋白质解折叠不一致。目前正在开展进一步的项目，以澄清这种不一致之处。

It is well-known that the hydrophobic effect is a critical factor for structural stability of proteins. The purpose of this project is to develop an experimental model for the hydrophobic effect. As a model, we investigated conformational equilibrium of simple chain molecules by using Raman spectroscopy. The most simple and ideal model is the trans gauche equilibrium of butane. We first target this system in aqueous solution. However, it was difficult to observe the equilibrium by Raman spectroscopy due to the low solubility of butane into water. During this project term, we succeed to observe qualitatively the equilibrium, indicating that the relative population of the gauche conformer increased compared with the organic solvent systems. The further experiments for the quantitative analysis are in progress. As another targets we investigated trans-gauche/gauche-gauche equilibrium of diethyl disulfide, which is a model for disulfide bonds for proteins. We elucidated the effect of temperature and pressure on the equilibrium, and discuss the phenomena in comparison with the conformational change of disulfide of a protein when it unfolds. The other research results were obtained for a simple peptide system. We target a simple alanine-rich peptide as a model molecule, which is suitable to observe the helix-coil equilibrium in water. Effect of pressure on the equilibrium showed that the relative population of helix form increases with increasing pressure. This behavior is apparently inconsistent with pressure-induced unfolding of protein. Further projects for elucidating the inconsistency are in progress.