Solvent-Directed Switch of a Left-Handed 10/12-Helix into a Right-Handed 12/10-Helix in Mixed β-Peptides

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• 作者：Prashanth Thodupunuri ; Sirisha KatukuriKallaganti V. S. Ramakrishna ; Gangavaram V. M. Sharma ; Ajit C. KunwarAkella V. S. Sarma ; Hans-Jörg Hofmann
• 刊名：Journal of Organic Chemistry
• 出版年：2017
• 出版时间：February 17, 2017
• 年：2017
• 卷：82
• 期：4
• 页码：2018-2031
• 全文大小：820K
• ISSN：1520-6904

文摘

Present study describes the synthesis and conformational analysis of β-peptides from C-linked carbo-β-amino acids [β-Caa_(l)] with a d-lyxo furanoside side chain and β-hGly in 1:1 alternation. NMR and CD investigations on peptides with an (S)-β-Caa_(l) monomer at the N-terminus revealed a right-handed 10/12-mixed helix. An unprecedented solvent-directed “switch” both in helical pattern and handedness was observed when the sequence begins with a β-hGly residue instead of a (S)-β-Caa_(l) constituent. NMR studies on these peptides in chloroform indicated a left-handed 10/12-helix, while the CD spectrum in methanol inferred a right-handed secondary structure. The NMR data for these peptides in CD₃OH showed the presence of a right-handed 12/10-helix. NMR investigations in acetonitrile indicated the coexistence of both helix types. Quantum chemical studies predicted a small energy difference of 0.3 kcal/mol between the two helix types, which may explain the possibility of solvent influence. Examples for a solvent-directed switch of both the H-bonding pattern and the handedness of foldamer helices are rare so far. A comparable solvent effect was not found in the corresponding peptides with (R)-β-Caa_(l) residues, where right-handed 12/10-helices are predominating.