Role of Ring-Constrained 纬-Amino Acid Residues in 伪/纬-Peptide Folding: Single-Conformation UV and IR Spectroscopy

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• 作者：Ryoji Kusaka ; Di Zhang ; Patrick S. Walsh ; Joseph R. Gord ; Brian F. Fisher ; Samuel H. Gellman ; Timothy S. Zwier
• 刊名：Journal of Physical Chemistry A
• 出版年：2013
• 出版时间：October 24, 2013
• 年：2013
• 卷：117
• 期：42
• 页码：10847-10862
• 全文大小：668K
• 年卷期：v.117,no.42(October 24, 2013)
• ISSN：1520-5215

文摘

The capped 伪/纬-peptide foldamers Ac-纬_ACHC-Ala-NH-benzyl (纬伪) and Ac-Ala-纬_ACHC-NH-benzyl (伪纬) were studied in the gas phase under jet-cooled conditions using single-conformation spectroscopy. These molecules serve as models for local segments of larger heterogeneous 1:1 伪/纬-peptides that have recently been synthesized and shown to form a 12-helix composed of repeating C12 H-bonded rings both in crystalline form and in solution [Guo, L.; et al. J. Am. Chem. Soc. 2009, 131, 16018]. The 纬伪 and 伪纬 peptide subunits are structurally constrained at the C尾鈥揅纬 bond of the 纬-residue with a cis-cyclohexyl ring and by an ethyl group at the C伪 position. These triamides are the minimum length necessary for the formation of the C12 H-bond. Resonant two-photon ionization (R2PI) provides ultraviolet spectra that have contributions from all conformational isomers, while IR-UV hole-burning (IR-UV HB) and resonant ion-dip infrared (RIDIR) spectroscopies are used to record single-conformation UV and IR spectra, respectively. Four and six conformers are identified in the R2PI spectra of the 纬伪 and 伪纬 peptides, respectively. RIDIR spectra in the NH stretch, amide I (C鈺怬 stretch), and amide II (NH bend) regions are compared with the predictions of density functional theory (DFT) calculations at the M05-2X/6-31+G* level, leading to definite assignments for the H-bonding architectures of the conformers. While the C12 H-bond is present in both 纬伪 and 伪纬, C9 rings are more prevalent, with seven of ten conformers incorporating a C9 H-bond involving in the 纬-residue. Nevertheless, comparison of the assigned structures of gas-phase 纬伪 and 伪纬 with the crystal structures for 纬伪 and larger 伪/纬-peptides reveals that the constrained 纬-peptide backbone formed by the C9 ring is structurally similar to that formed by the larger C12 ring present in the 12-helix. These results confirm that the ACHC/ethyl constrained 纬-residue is structurally preorganized to play a significant role in promoting C12 H-bond formation in larger 伪/纬-peptides.