β-Turn Preferences Induced by 2,3-Methanophenylalanine Chirality^†

The model dipeptides RCO-l-Pro-c3Phe-NHMe, where c3Phe stands for each of the four cyclopropane analogues of phenylalanine (2,3-methanophenylalanine), have been studied in solution by using 1H NMR and FT-IR spectroscopy and in the solid state by using X-ray diffraction. The conformational behavior of these compounds has been compared to that of the analogous Ac3c and l- or d-Phe-containing dipeptides. When associated to proline, the cyclopropane residues in the so-called i + 2 position exhibit a marked tendency to β-folding in solution, even in DMSO. The type II β-turn is generally favored, but the βI/βII-turn ratio depends both on the experimental conditions (solvent, solution, or solid state) and on the chirality of the c3Phe moiety, which rigidly fixes the orientation of the phenyl ring with respect to the peptide backbone. The (2S,3S)c3Phe residue, analogous to l-Phe with the χ1 angle constrained to about 0°, is the most propitious to βI-folding in the i + 2 position of a putative β-turn.本研究针对作为模型化合物的二肽RCO-L-脯氨酰-c3Phe-NHMe展开，其中环丙烷苯丙氨酸类似物（c3Phe）指代苯丙氨酸的四种环丙烷类似物（即2,3-亚甲基苯丙氨酸）。研究采用氢核磁共振（1H NMR）与傅里叶变换红外光谱（FT-IR）对其溶液状态进行表征，并通过X射线衍射（X-ray diffraction）分析其固态结构。随后将此类化合物的构象行为与含Ac3c以及L-或D-苯丙氨酸的同源二肽进行对比分析。当环丙烷残基与脯氨酸相连并处于所谓的i+2位时，即便在二甲亚砜（DMSO）溶剂中，其在溶液中仍表现出显著的β折叠（β-folding）倾向。II型β转角（type II β-turn）通常更占优势，但βI/βII转角（βI/βII-turn）的比值同时取决于实验条件（包括溶剂类型、溶液或固态环境）以及c3Phe片段的手性——后者可刚性固定苯环相对于肽主链的取向。其中(2S,3S)-c3Phe残基的χ1二面角（χ1 angle）被约束在约0°，与L-苯丙氨酸的结构特征一致，是最有利于在假定的β转角（putative β-turn）的i+2位形成βI折叠（βI-folding）的残基。