Department of Chemistry, University of Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland.
J Am Chem Soc. 2009 Oct 28;131(42):15474-82. doi: 10.1021/ja906466q.
The conformational stability of the polyproline II (PPII) helix with respect to the functional groups at the C- and N-termini was examined both experimentally and theoretically. Oligoprolines AcN-Pro-CONH(2) (1), HN-Pro-CONH(2) (2), AcN-Pro-CO(2)H (3), and HN-Pro-CO(2)H (4) with charged and capped termini served as model compounds, and the relative ease with which they switch from the PPII to the polyproline I (PPI) helix was used as a measure to analyze their conformational stabilities. CD spectroscopic studies demonstrate that a positively charged N-terminus and a negatively charged C-terminus destabilize the PPII helix and favor the PPI helix, whereas capped termini favor the PPII over the PPI helix. These experimental findings are supported by the energy differences between the PPII and PPI helices of oligoprolines 1-4 computed by ab initio methods including electron-correlation effects (second-order Møller-Plesset perturbation theory, MP2). Furthermore, these quantum-chemical calculations show that differences in charge-dipole interactions are responsible for the experimentally and computationally observed relative stabilities. Although these electrostatic interactions between the terminal charges and the amide dipoles stabilize both helices, they are significantly stronger in the PPI helix where the amide bonds are oriented almost linear to the helix axis as compared to the PPII helix in which the amides are nearly perpendicular to the axis. Moreover, we demonstrate that a negative charge at the C-terminus has a more pronounced effect on the relative stability as compared to a positive charge at the N-terminus due to destabilization of the PPII helix by repulsive interaction between the C-terminal carboxylate with the neighboring amide bond. Studies at different pH values verified the electrostatic nature of the observed effects and demonstrate how changes in the protonation state can be used to deliberately stabilize the PPII helix over the PPI helix or vice versa.
我们通过实验和理论研究考察了 C 端和 N 端官能团对聚脯氨酸 II (PPII) 螺旋构象稳定性的影响。带电荷和封端的寡脯氨酸 AcN-Pro-CONH(2) (1)、HN-Pro-CONH(2) (2)、AcN-Pro-CO(2)H (3) 和 HN-Pro-CO(2)H (4) 用作模型化合物，它们从 PPII 向聚脯氨酸 I (PPI) 螺旋转变的容易程度被用来分析它们的构象稳定性。圆二色光谱研究表明，带正电荷的 N 端和带负电荷的 C 端使 PPII 螺旋不稳定，有利于 PPI 螺旋，而封端使 PPII 螺旋优先于 PPI 螺旋。这些实验结果得到了通过包括电子相关效应（二阶 Møller-Plesset 微扰理论，MP2）在内的从头算方法计算的寡脯氨酸 1-4 的 PPII 和 PPI 螺旋之间的能量差的支持。此外，这些量子化学计算表明，末端电荷和酰胺偶极子之间的电荷-偶极相互作用的差异是实验和计算观察到的相对稳定性的原因。尽管这些静电相互作用稳定了两个螺旋，但在 PPI 螺旋中，酰胺键几乎与螺旋轴线性取向，而在 PPII 螺旋中，酰胺几乎垂直于螺旋轴，因此这些相互作用在 PPI 螺旋中要强得多。此外，我们证明，与 N 端带正电荷相比，C 端带负电荷对相对稳定性的影响更为显著，这是由于 C 端羧酸盐与相邻酰胺键之间的排斥相互作用使 PPII 螺旋失稳。在不同 pH 值下的研究证实了所观察到的效应的静电性质，并展示了质子化状态的变化如何可用于有意使 PPII 螺旋优先于 PPI 螺旋或反之亦然。
