Rothemund S, Krause E, Beyermann M, Dathe M, Bienert M, Hodges R S, Sykes B D, Sönnichsen F D
Institute of Molecular Pharmacology, Berlin, Germany.
Pept Res. 1996 Mar-Apr;9(2):79-87.
We recently described the local destabilizing effect of systematic double D-amino acid replacements for characterization of amphipathic helices in peptides. The objective of this study was to determine the destabilizing effect of two adjacent D-amino acids incorporated into the center of a single-stranded amphipathic alpha-helix by hydrogen exchange and guanidine hydrochloride denaturation studies in trifluoroethanol (TFE)/water. Data from guanidine hydrochloride titration experiments in the presence of 30% TFE suggest that double D-amino acid replacements at the center of the helix destabilize the secondary structure by 4.5 kJ/mol. While the exchange rate for one backbone proton was found to vary by a factor of 10 at the replacement position, the remaining backbone protons are not markedly influenced by double D-amino acid replacement. These results confirm the hypothesis that the energy of -4.5 kJ/mol per residue is a major contribution to the stability of helical peptides in water and in solvent mixtures of TFE/water.
我们最近描述了通过系统性双D-氨基酸替换对肽中两亲性螺旋进行表征的局部去稳定化效应。本研究的目的是通过在三氟乙醇（TFE）/水体系中进行氢交换和盐酸胍变性研究，确定掺入单链两亲性α-螺旋中心的两个相邻D-氨基酸的去稳定化效应。在30% TFE存在下进行的盐酸胍滴定实验数据表明，螺旋中心的双D-氨基酸替换使二级结构去稳定化4.5 kJ/mol。虽然发现在替换位置一个主链质子的交换速率变化了10倍，但其余主链质子并未受到双D-氨基酸替换的显著影响。这些结果证实了以下假设：每个残基-4.5 kJ/mol的能量是对螺旋肽在水和TFE/水溶剂混合物中稳定性的主要贡献。
