ALPHA-HELIX STABILIZATION BY NATURAL AND UNNATURAL AMINO-ACIDS WITH ALKYL SIDE-CHAINS
ALPHA-HELIX STABILIZATION BY NATURAL AND UNNATURAL AMINO-ACIDS WITH ALKYL SIDE-CHAINS
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DOI：
10.1073/pnas.88.12.5317
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
KALLENBACH, NR
中科院分区：
文献类型：
--
作者：
LYU, PC;SHERMAN, JC;KALLENBACH, NR
了解单个侧链在形成不同二级结构（如α-螺旋）中的作用将有助于从序列或从头蛋白质设计预测蛋白质结构。对天然和合成肽和蛋白质的实验和理论研究表明，各个侧链的螺旋形成潜力不同。四个脂肪族侧链存在于氨基酸的标准互补中：丙氨酸和亮氨酸是螺旋稳定的，而异亮氨酸和缬氨酸是弱不稳定的。我们已经合成了一系列的螺旋肽含有非天然的脂肪族侧链有两个到四个碳，探索一些参与α-螺旋稳定的因素和选择的自然设置的基础。我们发现，线性侧链与两个，三个，或四个碳是强烈的螺旋稳定的单个甲基丙氨酸和所有的线性侧链是更强的螺旋启动子比亮氨酸。此外，叔丁基侧链比异亮氨酸的仲丁基侧链、缬氨酸的异丙基侧链或甚至甘氨酸的非限制性侧链显著更螺旋不稳定。这些结果提供了实验证据，即由α-螺旋形成施加的侧链构象自由度的限制是侧链在稳定螺旋结构中的作用的主要组成部分。
Knowledge of the role of individual side chains in forming different secondary structures such as the alpha-helix would be useful for prediction of protein structure from sequence or de novo protein design. Experimental and theoretical studies on natural and synthetic peptides and proteins indicate that individual side chains differ in their helix-forming potential. Four aliphatic side chains occur in the standard complement of amino acids: alanine and leucine are helix stabilizing, whereas isoleucine and valine are weakly destabilizing. We have synthesized a series of helical peptides containing unnatural aliphatic side chains having two to four carbons to explore some of the factors involved in alpha-helix stabilization and the basis for selection of the natural set. We find that linear side chains with two, three, or four carbons are as strongly helix stabilizing as the single methyl in alanine and that all linear side chains are stronger helix promoters than leucine. In addition, a t-butyl side chain is significantly more helix destabilizing than the sec-butyl side chain of isoleucine, the isopropyl side chain of valine, or even the unrestricted side chain of glycine. These results provide experimental evidence that restriction in conformational freedom of a side chain imposed by alpha-helix formation is a major component of the role of a side chain in stabilizing helical structure.