Clustering of fluorine-substituted alcohols as a factor responsible for their marked effects on proteins and peptides
Clustering of fluorine-substituted alcohols as a factor responsible for their marked effects on proteins and peptides
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DOI：
10.1021/ja990833t
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发表时间：
1999-09-22
影响因子：
15
通讯作者：
Goto, Y
中科院分区：
文献类型：
--
作者：
Hong, DP;Hoshino, M;Goto, Y
在各种醇中，那些被氟取代的醇，如2，2，2-三氟乙醇（TFE）或3，3，3，3，3 '，3'，3 '-六氟-2-丙醇（HFIP），具有显著的诱导肽中α-螺旋结构形成和使蛋白质的天然结构变性的潜力。然而，这些醇发挥其作用的机制尚不清楚。蜂毒肽是一种蜂毒肽，在没有醇的情况下是解折叠的，但在加入醇后转化为α-螺旋结构。另一方面，将醇添加到β-乳球蛋白（一种主要的β-折叠蛋白）中，使分子变性并将其转化为α-螺旋结构。我们研究了几个因素在这些酒精诱导的转变中的作用，即，相对介电常数，强度的氢键水杨酸的pH滴定估计，和集群的醇分子的溶液X-射线散射测量。虽然相对介电常数和氢键强度被证实是重要的，他们没有解释显着的效果TFE和HFIP。X射线散射检测到的TFE或HFIP分子在酒精/水的混合物中的集群，最大值约为30%（v/v）的每种酒精。当TFE和HFIP诱导的构象转变与相应的醇/水混合物形成簇的程度作图时，对于蜂毒肽和β-乳球蛋白，TFE和HFIP诱导的转变曲线彼此一致，这表明醇分子的簇化是增强醇对蛋白质和肽的作用的重要因素。
Among Various alcohols, those substituted with fluorine, such as 2,2,2-trifluoroethanol (TFE) or 3,3,3,3',3',3'-hexafluoro-2-propanol (HFIP), have a marked potential to induce the formation of alpha-helical structures in peptides and to denature the native structures of proteins. However, the mechanism by which these alcohols exert their effects is unknown. Melittin, a bee venom peptide, is unfolded in the absence of alcohol, but is transformed to an alpha-helical structure upon addition of alcohols. On the other hand, addition of alcohols to beta-lactoglobulin, a predominantly beta-sheet protein, denatures the molecule and transforms it to an alpha-helical structure. We examined the role of several factors in these alcohol-induced transitions, i.e., relative dielectric constant, strength of hydrogen bond estimated by the pH titration of salicylic acid, and clustering of alcohol molecules measured by solution X-ray scattering. Although relative dielectric constant and hydrogen bond strength were confirmed to be important, they did not explain the marked effects of TFE and HFIP. X-ray scattering detected clusters of TFE or HFIP molecules in alcohol/water mixtures with a maximum at around 30% (v/v) of each alcohol. When the conformational transitions induced by TFE and HFIP were plotted against the extent of cluster formation by the corresponding alcohol/water mixtures, the TFE and HFIP-induced transition curves agreed with each other for both melittin and beta-lactoglobulin, This suggests that clustering of alcohol molecules is an important factor that enhances the effects of alcohols on proteins and peptides.