External chirality-triggered helicity control promoted by introducing a β-ala residue into the N-terminus of chiral peptides
External chirality-triggered helicity control promoted by introducing a β-ala residue into the N-terminus of chiral peptides
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DOI：
10.1021/bm0344001
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发表时间：
2004-07-01
影响因子：
6.2
通讯作者：
Komori, H
中科院分区：
文献类型：
--
作者：
Inai, Y;Komori, H
非共价手性多米诺骨牌效应（NCDE）被定义为3(10)-螺旋肽的所有n端上的手性相互作用，将通过使用外部手性为肽螺旋的结构控制提供一种独特的方法。另一方面，NCDE还没有被认为是有效的螺旋控制肽强烈倾向于单手螺旋感觉。我们的目的是利用两种非肽：h - β - ala -Delta(Z) ph -Aib-Delta(Z) ph -X*-(Delta(Z) ph -Aib)(2)- och3 [Delta(Z)Phe = α， β -二脱氢苯丙氨酸，Aib = α -氨基异丁酸]来促进肽螺旋度的NCDE，其中X*为单手性是l -亮氨酸(1)或l -苯丙氨酸(2)。核磁共振，红外和CD光谱以及能量计算表明，这两个肽单独形成右手3(10)-螺旋。在氯仿中，原始的CD振幅或信号，无论中心手性是否具有强烈的旋感偏好，都对外部手性信息做出敏感的反应。即添加的boc - l -氨基酸稳定了原来的右手螺旋，而相应的d -异构体使其不稳定或转化为左手螺旋。这些肽也被证明更有利于与外消旋体的l -异构体结合。虽然类似的螺旋控制被观察到类似的非肽携带一个n端Aib残基（Inai， Y.；等）。生物大分子2003,4。122)，目前的研究结果表明，β - ala残基取代n端显著改善了以前的NCDE，实现了更有效的螺旋度控制。肽2与BOC-(L或D)- pro - oh络合的半经验分子轨道计算合理地解释了外部手性引起的独特构象变化。
The noncovalent chiral domino effect (NCDE), defined as chiral interaction upon ail N-terminus of a 3(10)-helical peptide, will provide a unique method for structural control of a peptide helix through the use of external chirality. On the other hand, the NCDE has not been considered to be effective for the helicity control of peptides strongly favoring a one-handed screw sense. We here aim to promote the NCDE on peptide helicity using two types of nonapeptides: H-beta-Ala-Delta(Z)Phe-Aib-Delta(Z)Phe-X*-(Delta(Z)Phe-Aib)(2)-OCH3 [Delta(Z)Phe = alpha,beta-didehydrophenylalanine, Aib = alpha-aminoisobutyric acid], where X* as the single chirality is L-leucine (1) or L-phenylalanine (2). NMR, IR, and CD spectroscopy as well as energy calculation revealed that both peptides alone form a right-handed 3(10)-helix. The original CD amplitudes or signs in chloroform, irrespective of a strong screw-sense preference in the central chirality, responded sensitively to external chiral information. Namely added BOC-L-amino acid stabilized the original right-handed helix, while the corresponding D-isomer destabilized it or transformed it into a left-handed helix. These peptides were also shown to bind more favorably to an L-isomer from the racemate. Although similar helicity control was observed for analogous nonapeptides bearing an N-terminal Aib residue (Inai, Y.; et al. Biomacromolecules 2003, 4. 122), the present findings demonstrate that the N-terminal replacement by the beta-Ala residue significantly improves the previous NCDE to achieve more effective control of helicity. Semiempirical molecular orbital calculations on complexation of peptide 2 with BOC-(L or D)-Pro-OH reasonably explained the unique conformational change induced by external chirality.