Membrane partitioning: distinguishing bilayer effects from the hydrophobic effect.
Membrane partitioning: distinguishing bilayer effects from the hydrophobic effect.
复制标题
膜分配：区分双层效应和疏水效应。
DOI：
10.1021/bi00076a001
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
White,SH
中科院分区：
文献类型：
--
作者：
Wimley,WC;White,SH
摘要：非极性溶质从水到脂质双分子层转移的自由能通常由大的负焓而不是由疏水效应所期望的大的正熵所主导。这种常见的观察导致了“非经典”疏水效应的概念，以及“经典”疏水效应可能不会驱动许多双层体系中的分配的想法。我们通过测量色氨酸侧链类似物进入脂质双层和散装环己烷的热容量变化表明，疏水效应起着至关重要的作用，而不管大的负焓。结果强调，体相测量不足以描述双层分配。所描述的实验方法对于分析广泛的生物重要分子的双层相互作用通常是有用的。药物设计的一个重要目标是有效地穿过膜屏障。实现这一目标的有效策略的发展取决于对非极性和两亲分子划分为脂质双分子层的原则的清晰理解。膜蛋白的插入和折叠、肽介导的膜融合以及抗生素肽的作用的实验研究也在很大程度上依赖于这些原理。划分的主要驱动力被广泛认为是疏水效应，因为在划分成大块非极性相时观察到疏水效应。然而，在过去20年中积累的证据（Huang & Charlton, 1972; White, 1976, 1977； Simon等人，1977,1979;Seelig & Ganz, 1991; Marqusee & Dill, 1986）表明，双层分配要复杂得多，这可能是由于双层是各向异性和化学非均相的界面相（Seelig & Seelig, 1977； Buldt等人，1978;Wiener & White, 1992）所预料的。主要的
Revised Manuscript Received May 10, 1993 abstract: The free energy of transfer of nonpolar solutes from water to lipid bilayers is often dominated by a large negative enthalpy rather than the large positive entropy expected from the hydrophobic effect. This common observation has led to the concept of the “nonclassical” hydrophobic effect and the idea that the “classical” hydrophobic effect may not drive partitioning in many bilayer systems. We show through measurements of the heat capacity changes associated with the partitioning of tryptophan side-chain analogs into lipid bilayers and into bulk cyclohexane that the hydrophobic effect plays a crucial role regardless of the large negative enthalpy. The results emphasize that bulk-phasemeasurements are inadequate for describing bilayer partitioning. The experimental approach described should be generally useful for analyzing the bilayer interactions of a broad range of biologically important molecules.An important goal in the design of drugs is efficient movement across membrane barriers. The development of effective strategies to accomplish this goaldepends upon a clear understanding of the principles that govern the partitioning of nonpolar and amphipathic molecules into lipid bilayers. Experimental studies of the insertion and folding of membrane proteins, peptide-mediated membrane fusion, and the action of antibiotic peptides rely heavily on these principles as well. The major driving force for partitioning is widely assumed to be thehydrophobic effect as observed for partitioning into bulk nonpolar phases. However, evidence has accumulated during the past 20 years (Huang & Charlton, 1972; White, 1976, 1977; Simon et al., 1977, 1979; Seelig & Ganz, 1991; Marqusee & Dill, 1986) indicating that bilayer partitioning is much more complicated, as might have been anticipated from the fact that bilayers are anisotropic and chemically heterogeneous interfacial phases (Seelig & Seelig, 1977; Buldt et al., 1978; Wiener & White, 1992). The main