Cis鈥?i>Trans Amide Bond Rotamers in 尾-Peptoids and Peptoids: Evaluation of Stereoelectronic Effects in Backbone and Side Chains

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• 作者：Jonas S. Laursen ; Jens Engel-Andreasen ; Peter Fristrup ; Pernille Harris ; Christian A. Olsen
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：February 20, 2013
• 年：2013
• 卷：135
• 期：7
• 页码：2835-2844
• 全文大小：461K
• 年卷期：v.135,no.7(February 20, 2013)
• ISSN：1520-5126

文摘

Non-natural peptide analogs have significant potential for the development of new materials and pharmacologically active ligands. One such architecture, the 尾-peptoids (N-alkyl-尾-alanines), has found use in a variety of biologically active compounds but has been sparsely studied with respect to folding propensity. Thus, we here report an investigation of the effect of structural variations on the cis鈥?i>trans amide bond rotamer equilibria in a selection of monomer model systems. In addition to various side chain effects, which correlated well with previous studies of 伪-peptoids, we present the synthesis and investigation of cis鈥?i>trans isomerism in the first examples of peptoids and 尾-peptoids containing thioamide bonds as well as trifluoroacetylated peptoids and 尾-peptoids. These systems revealed an increase in the preference for cis-amides as compared to their parent compounds and thus provide novel strategies for affecting the folding of peptoid constructs. By using NMR spectroscopy, X-ray crystallographic analysis, and density functional theory calculations, we present evidence for the presence of thioamide鈥揳romatic interactions through C_sp²鈥揌路路路S_amide hydrogen bonding, which stabilize certain peptoid conformations.