Relationship of Sidechain Hydrophobicity and α-Helical Propensity on the Stability of the Single-stranded Amphipathic α-Helix
Relationship of Sidechain Hydrophobicity and α-Helical Propensity on the Stability of the Single-stranded Amphipathic α-Helix
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DOI：
10.1002/psc.310010507
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发表时间：
1995-09-01
影响因子：
2.1
通讯作者：
Hodges, Robert S.
中科院分区：
文献类型：
--
作者：
Monera, Oscar D.;Sereda, Terrance J.;Hodges, Robert S.
本研究的目的是确定α-螺旋倾向和侧链疏水性对两亲性α-螺旋稳定性的影响。因此，已经合成了一系列18个残基的两亲性α-螺旋肽作为模型系统，其中所有20个氨基酸残基在两亲性α-螺旋的疏水面上被取代。在这些实验中，对同一组肽类似物测量所有三个参数（侧链疏水性、α-螺旋倾向和螺旋稳定性）。对于仅相差一个氨基酸残基的这些肽类似物，在反相柱上，最大（Ala）和最小（Gly）α-螺旋类似物之间的α-螺旋倾向差异为0.96千卡/摩尔，最大（Phe）和最小（Asp）保留类似物之间的差异为12.1分钟，最稳定的类似物（Leu）和最不稳定的类似物（Asp）之间的熔解温度差为32.3 ℃。结果表明，氨基酸侧链的疏水性和α-螺旋倾向彼此不相关，但各自有助于两亲性α-螺旋的稳定性。更重要的是，α-螺旋倾向和侧链疏水性以约2：1的比率的组合效应与α-螺旋稳定性具有最佳相关性。这些结果表明，α-螺旋倾向和侧链疏水性应考虑在设计的α-螺旋蛋白质与所需的稳定性。
The aim of the present investigation is to determine the effect of alpha-helical propensity and sidechain hydrophobicity on the stability of amphipathic alpha-helices. Accordingly, a series of 18-residue amphipathic alpha-helical peptides has been synthesized as a model system where all 20 amino acid residues were substituted on the hydrophobic face of the amphipathic a-helix. In these experiments, all three parameters (sidechain hydrophobicity, alpha-helical propensity and helix stability) were measured on the same set of peptide analogues. For these peptide analogues that differ by only one amino acid residue, there was a 0.96 kcal/mole difference in alpha-helical propensity between the most (Ala) and the least (Gly) alpha-helical analogue, a 12.1-minute difference between the most (Phe) and the least (Asp) retentive analogue on the reversed-phase column, and a 32.3 degrees C difference in melting temperatures between the most (Leu) and the least (Asp) stable analogue. The results show that the hydrophobicity and alpha-helical propensity of an amino acid sidechain are not correlated with each other, but each contributes to the stability of the amphipathic alpha-helix. More importantly, the combined effects of alpha-helical propensity and sidechain hydrophobicity at a ratio of about 2: 1 had optimal correlation with alpha-helix stability. These results suggest that both alpha-helical propensity and sidechain hydrophobicity should be taken into consideration in the design of alpha-helical proteins with the desired stability.