Misra Rajkumar, Raja K Muruga Poopathi, Hofmann Hans-Jörg, Gopi Hosahudya N
Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, 411 008, India.
Department of Physical Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, 625 021, India.
Chemistry. 2017 Nov 21;23(65):16644-16652. doi: 10.1002/chem.201703871. Epub 2017 Nov 3.
The most important natural α- and 3 -helices are stabilized by unidirectional intramolecular hydrogen bonds along the helical cylinder. In contrast, we report here on 12/10-helical conformations with alternately changing hydrogen-bond directionality in sequences of α,γ-hybrid peptides P1-P5 [P1: Boc-Ala-Aic-Ala-Aic-COOH; P2: Boc-Leu-Aic-Leu-Aic-OEt; P3: Boc-Leu-Aic-Leu-Aic-Leu-Aic-Aib-OMe; P4: Boc-Ala-Aic-Ala-Aic-Ala-Aic-Ala-OMe; P5: Boc-Leu-Aic-Leu-Aic-Leu-Aic-Leu-Aic-Aib-OMe; Aic=4-aminoisocaproic acid, Aib=2-aminoisobutyric acid] composed of natural α-amino acids and the achiral γ -dimethyl substituted γ-amino acid Aic in solution and in single crystals. The helical conformations are stabilized by alternating i→i+3 and i→i-1 intramolecular hydrogen bonds. The experimental data are supported by ab initio MO calculations. Surprisingly, replacing the natural α-amino acids of the sequence by the achiral dialkyl amino acid Ac c [P6: Boc-Ac c-Aic-Ac c-Aic-Ac c-Aic-Ac c-Aic-Ac c-CONHMe; Ac c = 1-aminocyclohexane-1-carboxylic acid] led to a 12-helix with unidirectional hydrogen bonds showing an entirely different backbone conformation. The results presented here emphasize the influence of the structure of the α-amino acid residues in dictating the helix types in α,γ-hybrid peptide foldamers and demonstrate the consequences for folding of small structural variations in the monomers.
最重要的天然α-螺旋和3-螺旋通过沿螺旋柱的单向分子内氢键得以稳定。相比之下，我们在此报告了α,γ-杂合肽P1 - P5序列（P1：Boc - Ala - Aic - Ala - Aic - COOH；P2：Boc - Leu - Aic - Leu - Aic - OEt；P3：Boc - Leu - Aic - Leu - Aic - Leu - Aic - Aib - OMe；P4：Boc - Ala - Aic - Ala - Aic - Ala - Aic - Ala - OMe；P5：Boc - Leu - Aic - Leu - Aic - Leu - Aic - Leu - Aic - Aib - OMe；Aic = 4 - 氨基异己酸，Aib = 2 - 氨基异丁酸）在溶液和单晶中形成的12/10 - 螺旋构象，其氢键方向性交替变化。这些螺旋构象通过交替的i→i + 3和i→i - 1分子内氢键得以稳定。实验数据得到了从头算MO计算的支持。令人惊讶的是，用非手性二烷基氨基酸Acc取代序列中的天然α-氨基酸（P6：Boc - Acc - Aic - Acc - Aic - Acc - Aic - Acc - Aic - Acc - CONHMe；Acc = 1 - 氨基环己烷 - 1 - 羧酸）导致形成具有单向氢键的12 - 螺旋，呈现出完全不同的主链构象。此处呈现的结果强调了α-氨基酸残基结构在决定α,γ-杂合肽折叠体中的螺旋类型方面的影响，并证明了单体中小的结构变化对折叠的影响。
