Structural Characterizations of Oligopyridyl Foldamers, 伪-Helix Mimetics

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• 作者：Jana Sopkova-de Oliveira Santos ; Anne Sophie Voisin-Chiret ; Gregory Burzicki ; Laure Sebaoun ; Muriel Sebban ; Jean-Fran莽ois Lohier ; R茅mi Legay ; Hassan Oulyadi ; Ronan Bureau ; Sylvain Rault
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2012
• 出版时间：February 27, 2012
• 年：2012
• 卷：52
• 期：2
• 页码：429-439
• 全文大小：559K
• 年卷期：v.52,no.2(February 27, 2012)
• ISSN：1549-960X

文摘

Protein鈥損rotein interactions are central to many biological processes, from intracellular communication to cytoskeleton assembly, and therefore represent an important class of targets for new therapeutics. The most common secondary structure in natural proteins is an 伪-helix. Small molecules seem to be attractive candidates for stabilizing or disrupting protein鈥損rotein interactions based on 伪-helices. In our study, we assessed the ability of oligopyridyl scaffolds to mimic the 伪-helical twist. The theoretical as well as experimental studies (X-ray diffraction and NMR) on conformations of bipyridines in the function of substituent and pyridine nitrogen positions were carried out. Furthermore, the experimental techniques showed that the conformations observed in bipyridines are maintained within a longer oligopyridyl scaffold (quaterpyridines). The alignment of the synthesized quaterpyridine with two methyl substituents showed that it is an 伪-helix foldamer; their methyl groups overlap very well with side chain positions, i and i + 3, of an ideal 伪-helix.