New strategies for the design of folded peptoids revealed by a survey of noncovalent interactions in model systems.
New strategies for the design of folded peptoids revealed by a survey of noncovalent interactions in model systems.
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DOI：
10.1021/ja907184g
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发表时间：
2009-11-18
影响因子：
15
通讯作者：
Blackwell, Helen E.
中科院分区：
文献类型：
--
作者：
Gorske, Benjamin C.;Stringer, Joseph R.;Bastian, Brent L.;Fowler, Sarah A.;Blackwell, Helen E.
在构建离散折叠的类肽结构中，控制主链顺式和反式酰胺或N-取代甘氨酸低聚物之间的平衡是一个重大的挑战。通过对一系列单体类肽模型体系的分析，我们开发了一种新的、通用的控制类肽构象的策略，这些策略利用局部非共价相互作用来调节主链酰胺的旋转体平衡，包括n→π*、空间和氢键相互作用。实施这些策略所需的化学功能通常限于类肽侧链，在侧链N-α-Carbon上保持手性，并与标准的类肽合成技术完全兼容。我们对类肽模型系统的研究也阐明了溶剂如何影响各种侧链-主链相互作用，揭示了类肽中这些非共价相互作用的基本方面，这些方面以前基本上没有描述过。作为单体模型系统的验证，我们将这项研究的范围扩大到包括类肽低聚物，现在已经证明了局部空间和n-→π*相互作用在决定较大的折叠类肽的结构中的重要性。这一新的模块化设计策略指导了含有1-萘乙基侧链的类肽的构建，我们表明，这可以被用来有效地从类肽主干上消除反式-酰胺旋转异构体，产生迄今报道的构象最均匀的类肽结构，就酰胺旋转异构体而言。总体而言，这项研究为构建离散折叠的类肽和结构偏向的类肽文库提供了一套有价值的和可扩展的设计工具，并应该塑造我们对类肽折叠的理解。
Controlling the equilibria between backbone cis- and trans-amides in peptoids, or N-substituted glycine oligomers, constitutes a significant challenge in the construction of discretely folded peptoid structures. Through the analysis of a set of monomeric peptoid model systems, we have developed new and general strategies for controlling peptoid conformation that utilize local noncovalent interactions to regulate backbone amide rotameric equilibria, including n→π*, steric, and hydrogen bonding interactions. The chemical functionalities required to implement these strategies are typically confined to the peptoid side chains, preserve chirality at the side chain N-α-carbon known to engender peptoid structure, and are fully compatible with standard peptoid synthesis techniques. Our examinations of peptoid model systems have also elucidated how solvents affect various side chain-backbone interactions, revealing fundamental aspects of these noncovalent interactions in peptoids that were largely uncharacterized previously. As validation of our monomeric model systems, we extended the scope of this study to include peptoid oligomers and have now demonstrated the importance of local steric and n→π* interactions in dictating the structures of larger, folded peptoids. This new, modular design strategy has guided the construction of peptoids containing 1-naphthylethyl side chains, which we show can be utilized to effectively eliminate trans-amide rotamers from the peptoid backbone, yielding the most conformationally homogeneous class of peptoid structures yet reported in terms of amide rotamerism. Overall, this research has afforded a valuable and expansive set of design tools for the construction of both discretely folded peptoids and structurally-biased peptoid libraries, and should shape our understanding of peptoid folding.
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影响因子：
15
作者：
DeRider, ML;Wilkens, SJ;Markley, JL
通讯作者：
Markley, JL
DOI：
10.1021/jo8023363
发表时间：
2009-02-20
期刊：
The Journal of organic chemistry
影响因子：
--
作者：
Fowler SA;Luechapanichkul R;Blackwell HE
通讯作者：
Blackwell HE
影响因子：
15
作者：
Hara, T;Durell, SR;Appella, DH
通讯作者：
Appella, DH
DOI：
10.1073/pnas.95.8.4309
发表时间：
1998-04-14
影响因子：
11.1
作者：
Armand, P;Kirshenbaum, K;Bradley, EK
通讯作者：
Bradley, EK
影响因子：
5.2
作者：
Gorske, BC;Jewell, SA;Blackwell, HE
通讯作者：
Blackwell, HE