A highly stable short α-helix constrained by a main-chain hydrogen-bond surrogate
A highly stable short α-helix constrained by a main-chain hydrogen-bond surrogate
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DOI：
10.1021/ja0466659
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发表时间：
2004-10-06
影响因子：
15
通讯作者：
Arora, PS
中科院分区：
文献类型：
--
作者：
Chapman, RN;Dimartino, G;Arora, PS
在此，我们描述了一种制备人工α-螺旋的策略，包括用共价键取代主链中的一个氢键。为了尽可能接近地模拟CO···H-N氢键，我们设想了CX-Y-N类型的共价键，其中X和Y是通过烯烃复分解反应连接的两个碳原子。我们的研究结果表明，在生理条件下，用碳-碳键取代短肽N-末端的theiandi+ 4残基之间的氢键会导致高度稳定的受限α-螺旋，如CD和NMR光谱所示。这种策略的优点是它允许获得短α-螺旋，同时严格保留生物分子相互作用所需的分子识别表面。
Herein we describe a strategy for the preparation of artificial α-helices involving replacement of one of the main-chain hydrogen bonds with a covalent linkage. To mimic the CO···H−N hydrogen bond as closely as possible, we envisioned a covalent bond of the type CX−Y−N, where X and Y are two carbon atoms connected through an olefin metathesis reaction. Our results demonstrate that the replacement of a hydrogen bond between theiandi+ 4 residues at the N-terminus of a short peptide with a carbon−carbon bond results in a highly stable constrained α-helix at physiological conditions as indicated by CD and NMR spectroscopies. The advantage of this strategy is that it allows access to short α-helices with strict preservation of molecular recognition surfaces required for biomolecular interactions.