鈥淏ridged鈥?n鈫捪€* Interactions Can Stabilize Peptoid Helices

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• 作者：Benjamin C. Gorske ; Ryan C. Nelson ; Zara S. Bowden ; Turner A. Kufe ; Adam M. Childs
• 刊名：Journal of Organic Chemistry
• 出版年：2013
• 出版时间：November 15, 2013
• 年：2013
• 卷：78
• 期：22
• 页码：11172-11183
• 全文大小：499K
• 年卷期：v.78,no.22(November 15, 2013)
• ISSN：1520-6904

文摘

Peptoids are an increasingly important class of peptidomimetic foldamers comprised of N-alkylglycine units that have been successfully developed as antimicrobial agents, lung surfactant replacements, enzyme inhibitors, and catalysts, among many other applications. Since peptoid secondary structures can be crucial to their desired functions, significant efforts have been devoted to developing means of modularly controlling peptoid backbone amide cis鈥?i>trans isomerism using side chains. Strategic engineering of interactions between side chain aromatic rings and backbone cis-amides (n鈫捪€*_Ar interactions) is an attractive strategy for stabilizing helical structures in N-a-chiral aromatic peptoids, which are among the most utilized classes of structured peptoids. Herein, we report the first detailed computational and experimental study of n鈫捪€*_Ar interactions in models of peptoids containing backbone thioamides, which we term 鈥渢hiopeptoids鈥? Our work has revealed that these interactions significantly affect amide rotamerism in both peptoid and thiopeptoid models via a newly characterized 鈥渂ridged鈥?mode of interaction mediated by the N-伪-C鈥揌 蟽 orbitals. Overall, this work elucidates new strategies for controlling both peptoid and thiopeptoid folding and suggests that thiopeptoids will be highly structured and therefore potentially useful as therapeutics, biological probes, and nanostructural engineering elements.