Chirality effects on the intrinsic acidity of oligopeptides have been studied using a pair of stereoisomeric tripeptides containing two alanine (A) residues and either an L- or a d-cysteine, ACA and A^dCA, where the C-terminus is amidated. The gas-phase acidities were determined by mass spectrometry measurements. The extended kinetic method yielded the deprotonation enthalpy (Δ_acidH) and the gas-phase acidity (Δ_acidG) of ACA to be 328.0 and 322.7 kcal/mol (1372.4 and 1350.2 kJ/mol), and of A^dCA to be 327.8 and 322.4 kcal/mol (1371.5 and 1348.9 kJ/mol), respectively. Although the quantitative difference is small, the branching ratio bracketing experiments clearly indicate that A^dCA is a stronger gas-phase acid than ACA. Conformations were obtained via a step-wise conformational search, followed by geometry and frequency calculations at the B3LYP/6-311 + G (d,p) level of theory. Theoretical gas-phase acidities are in good agreement with the experiments, which also suggests that A^dCA is a stronger gas-phase acid. The enhanced acidity of the d-cysteine containing peptide is likely due to the adoption of a unique bent conformation upon deprotonation at the thiol group, which enables more favorable hydrogen bonding interactions within the peptide ion. The findings imply that chirality change on a single amino acid residue may have a notable effect on the biochemical properties of peptides.

已经使用一对立体异构三肽研究了手性对寡肽内在酸度的影响，这些三肽包含两个丙氨酸 (A) 残基和一个 L-或一个d-半胱氨酸、ACA 和 A ^d CA，其中 C 端被酰胺化。气相酸度通过质谱测量确定。扩展动力学方法得到ACA的去质子化焓 ( Δ _acid H ) 和气相酸度 ( Δ _acid G ) 为 328.0 和 322.7 kcal/mol (1372.4 和 1350.2 kJ/mol)，A ^dCA 分别为 327.8 和 322.4 kcal/mol（1371.5 和 1348.9 kJ/mol）。尽管数量上的差异很小，但支化比括号实验清楚地表明，A ^d CA 是比 ACA 更强的气相酸。通过逐步构象搜索获得构象，然后在 B3LYP/6-311 + G (d,p) 理论水平进行几何和频率计算。理论气相酸度与实验非常吻合，这也表明 A ^d CA 是更强的气相酸。d的增强酸度含-半胱氨酸的肽可能是由于在硫醇基团去质子化时采用了独特的弯曲构象，这使得肽离子内的氢键相互作用更有利。这些发现意味着单个氨基酸残基的手性变化可能对肽的生化特性产生显着影响。