HYDROPHILICITY OF POLAR AMINO-ACID SIDE-CHAINS IS MARKEDLY REDUCED BY FLANKING PEPTIDE-BONDS
HYDROPHILICITY OF POLAR AMINO-ACID SIDE-CHAINS IS MARKEDLY REDUCED BY FLANKING PEPTIDE-BONDS
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DOI：
10.1016/0022-2836(88)90540-2
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发表时间：
1988-04-05
影响因子：
5.6
通讯作者：
ROSEMAN, MA
中科院分区：
文献类型：
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作者：
ROSEMAN, MA
几个氨基酸侧链亲水性尺度已被设计的基础上获得的游离氨基酸或侧链类似物的溶解度和水/有机溶剂分配数据。在几乎所有的情况下，这些规模是基于结构加和性假设：它已被假定为氨基酸侧链的转移自由能是相同的，在这些模型化合物，因为它们是在一个多肽。这种假设很可能是错误的。在本研究中，氨基酸侧链的加和性的偏差证明通过比较理论推导的规模，这是基于结构加和性，与实验推导的规模获得N-乙酰氨基酸胺。结果表明，侧翼的肽键显着降低了极性侧链的亲水性，在pH 7.0下，带电侧链的偏差高达几千卡路里（1千卡= 4.184千焦）。进一步的计算表明，这些偏差是由于极性官能团的不利转移自由能降低了40 - 85%。此外，邻近的母体分子（N-乙酰基甘氨酸酰胺）中的酰胺键的亲水性降低了36%的-CONH-骨架单元。这种减少预计是多肽骨架内部-CONH-单位的两倍。这些观察结果的重要性在于：（1）只有用模型肽才能获得有效的亲水性尺度;（2）在所有溶剂系统中，包括被认为模拟膜内部的非极性溶剂，预期会偏离加和性;（3）多肽自发插入膜可能比以前认为的更容易发生。为了估计侧链和多肽骨架从水转移到脂质双层内部的自由能，本研究的结果被用来构建基于水和非极性溶剂之间的溶质分配的亲水性尺度。亲水尺度的有效性，是基于其他标准比溶解度和水/有机溶剂分配数据进行了讨论。
Several amino acid side-chain hydropathy scales have been devised on the basis of solubility and water/organic solvent partitioning data obtained with free amino acids or side-chain analogs. In nearly all cases, these scales are based upon the structure-additivity assumption: it has been assumed that the transfer free energies of the amino acid side-chains are the same in these model compounds as they are in a polypeptide. This assumption is probably wrong. In the present study, deviations from additivity for amino acid side-chains are demonstrated by comparing a theoretically derived scale, which is based on structure-additivity, with an experimentally derived scale obtained with N-acetylamino acid amines. The results show that the flanking peptide bonds dramatically reduce the hydrophilicity of the polar side-chains, with deviations up to several kilocalories (1 kcal = 4.184 kJ) for the charged side-chains at pH 7.0. Further calculation shows that these deviations are due to reductions of 40 to 85% in the unfavorable transfer free energy of the polar functional groups. In addition, proximity of the neighboring amide bonds in the parent molecule (N-acetylglycine amide) decreases the hydrophilicity of the -CONH-backbone unit by 36%. This decrease is expected to be twice as large for -CONH- units in the interior of a polypeptide backbone. The significance of these observations is: (1) valid hydropathy scales can be obtained only with model peptides; (2) deviations from additivity are expected in all solvent systems, including non-polar solvents that are thought to mimic the interior of a membrane: (3) the spontaneous insertion of polypeptides into membrane is likely to occur much more readily than has been previously thought. In order to estimate the free energy of transferring the side-chains and the polypeptide backbone from water to the interior of a lipid bilayer, the results of this study are used to construct a hydropathy scale based upon the partitioning of solutes between water and non-polar solvents. The validity of hydropathy scales that are based on criteria other than solubility and water/organic solvent partitioning data is also discussed.