Coexistence of Left- and Right-Handed 12/10-Mixed Helices in Cyclically Constrained β-Peptides and Directed Formation of Single-Handed Helices upon Site-Specific Methylation
Coexistence of Left- and Right-Handed 12/10-Mixed Helices in Cyclically Constrained β-Peptides and Directed Formation of Single-Handed Helices upon Site-Specific Methylation
复制标题
循环约束 β 肽中左手和右手 12/10 混合螺旋的共存以及位点特异性甲基化时单手螺旋的定向形成
DOI：
10.1021/acs.jpca.0c03545
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Zwier, Timothy S.
中科院分区：
文献类型：
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作者：
Blodgett, Karl N.;Jang, Geunhyuk;Kim, Sojung;Kim, Min Kyung;Choi, Soo Hyuk;Zwier, Timothy S.
本文用构象特异性红外-紫外双共振方法研究了中性β-肽折叠体系列Ac-（ACHC）n-NHBn（n= 2-4）在气相中固有的构象选择性。环约束手性β-氨基酸cis-2-aminocyclohexane carboxylic acid（ACHC）被设计为使左右手螺旋在能量上接近。比较的红外光谱在NH拉伸和酰胺I/II区域的DFT计算的预测导致明确的分配的六个观察到的构象的分子在这一系列中，而确证计算和光谱的证据，提供了试探性的分配剩余的两个构象的IR数据没有记录。所观察到的结构属于两个构象家族之一：右手12/10混合螺旋或其“帽破坏”左手螺旋类似物，与显着的人口共存。还测试了在二肽（n= 2）水平上的环己烷骨架上的位点特异性和立体特异性甲基化，作为空间锁定预定环己烷椅式构象的手段。这些替换被证明是一种选择性地驱动一个螺旋方向或另一个螺旋方向的形成的手段。计算的相对能量和自由能的分子的所有可能的结构提供了强有力的支持证据，ACHC残基的刚性赋予不寻常的稳定性的12/10混合螺旋构象，无论当地的环境，温度，或C-末端封端单元。同时存在的双手螺旋提供了独特的机会，为未来的研究，他们的相互转换。
The inherent conformational preferences of the neutral β–peptide foldamer series, Ac-(ACHC)n-NHBn,n= 2–4, are studied in the gas phase using conformation-specific IR–UV double resonance methods. The cyclically constrained chiral β-amino acidcis-2-aminocyclohexane carboxylic acid (ACHC) is designed to bring both right- and left-handed helices into close energetic proximity. Comparison of the infrared spectra in the NH stretch and amide I/II regions with the predictions of DFT calculations lead to the unambiguous assignment of four out of the six observed conformations of the molecules in this series, while corroborating computational and spectral evidence, affords tentative assignments of the remaining two conformers for which IR data were not recorded. The observed structures fall into one of two conformational families: a right-handed 12/10-mixed helix or its “cap-disrupted” left-handed helical analogue, which coexist with significant populations. Site-specific and stereospecific methylation on the cyclohexane backbone at the dipeptide (n= 2) level is also tested as a means to sterically lock in a predetermined cyclohexane chair conformation. These substitutions are proven to be a means of selectively driving formation of one helical screw sense or the other. Calculated relative energies and free energies of all possible structures for the molecules provide strong supporting evidence that the rigid nature of the ACHC residue confers unusual stability to the 12/10-mixed helix conformation, regardless of local environment, temperature, or C-terminal capping unit. The simultaneous presence of both handed helices offers unique opportunities for future studies of their interconversion.