Extraordinarily robust polyproline type I peptoid helices generated via the incorporation of α-chiral aromatic N-1-naphthylethyl side chains.
Extraordinarily robust polyproline type I peptoid helices generated via the incorporation of α-chiral aromatic N-1-naphthylethyl side chains.
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通过掺入 α-手性芳香族 N-1-萘乙基侧链生成极其坚固的聚脯氨酸 I 型类肽螺旋。
DOI：
10.1021/ja204755p
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发表时间：
2011-10-05
影响因子：
15
通讯作者：
Blackwell, Helen E.
中科院分区：
文献类型：
--
作者：
Stringer, Joseph R.;Crapster, J. Aaron;Guzei, Ilia A.;Blackwell, Helen E.
类肽，或N-取代甘氨酸的低聚物，是一类折叠体，自近二十年前问世以来，已显示出非凡的功能潜力。然而，生成明确的类肽二级结构仍然是一项艰巨的任务。这种挑战部分是由于缺乏对类肽序列-结构关系的透彻理解，因此对类肽折叠过程的理解不完全。我们试图通过系统研究类肽中的非共价相互作用和能够进行这种相互作用的新型酰胺侧链的设计来描绘序列-结构关系。本文报道了一系列（S）-N-（1-萘乙基）甘氨酸（Ns 1 npe）类肽同源寡聚体的合成，并通过X射线晶体学、核磁共振和圆二色谱（CD）对其结构进行了详细的分析。发现这些类肽中有四种在固态下采用明确定义的结构，二面角与在聚脯氨酸I型（PPI）肽螺旋和具有α-手性侧链的类肽中观察到的二面角相似。代表性的Nslnpe四聚体的X-射线晶体结构揭示了全顺式酰胺螺旋，每圈约有三个残基，螺距约为6.0 μ m。2D-NMR分析的长度依赖性Nslnpe系列表明，这些类肽具有非常高的整体骨架酰胺Kcis/transs值在乙腈中，在溶液中的构象均匀的结构的指示。此外，CD光谱研究的Nslnpe均低聚物在乙腈和甲醇中揭示了一个惊人的长度依赖性增加，每个酰胺的椭圆度。这些Ns 1 npe螺旋代表了最稳健的拟肽螺旋被报道，并纳入（S）-N-（1-萘乙基）甘氨酸提供了一种新的方法，在这类重要的折叠体中产生稳定的螺旋结构。
Peptoids, or oligomers of N-substituted glycines, are a class of foldamers that have shown extraordinary functional potential since their inception nearly two decades ago. However, the generation of well-defined peptoid secondary structures remains a difficult task. This challenge is due, in part, to the lack of a thorough understanding of peptoid sequence-structure relationships and consequently, an incomplete understanding of the peptoid folding process. We seek to delineate sequence-structure relationships through the systematic study of noncovalent interactions in peptoids and the design of novel amide side chains capable of such interactions. Herein, we report the synthesis and detailed structural analysis of a series of (S)-N-(1-naphthylethyl)glycine (Ns1npe) peptoid homooligomers by X-ray crystallography, NMR and circular dichroism (CD) spectroscopy. Four of these peptoids were found to adopt well-defined structures in the solid state, with dihedral angles similar to those observed in polyproline type I (PPI) peptide helices and in peptoids with α-chiral side chains. The X-ray crystal structure of a representative Ns1npe tetramer revealed an all cis-amide helix, with approximately three residues per turn, and a helical pitch of approximately 6.0 Å. 2D-NMR analysis of the length-dependent Ns1npe series showed that these peptoids have very high overall backbone amide Kcis/trans values in acetonitrile, indicative of conformationally homogeneous structures in solution. Additionally, CD spectroscopy studies of the Ns1npe homooligomers in acetonitrile and methanol revealed a striking length-dependent increase in ellipticity per amide. These Ns1npe helices represent the most robust peptoid helices to be reported, and the incorporation of (S)-N-(1-naphthylethyl)glycines provides a new approach for the generation of stable helical structure in this important class of foldamers.
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影响因子：
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作者：
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影响因子：
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