A Simple Model System for the Study of Carbohydrate−Aromatic Interactions

University of Milan, Milano, Lombardy, Italy
Journal of the American Chemical Society (Impact Factor: 12.11). 04/2007; 129(10):2890-900. DOI: 10.1021/ja066633g
Source: PubMed


A molecular scaffold was identified which enables the establishment of intramolecular interactions between a monosaccharide and a nearby phenyl ring. A group of molecules containing four different monosaccharides (glucose, galactose, N-acetyl-glucosamine, and N-acetyl-galactosamine) was synthesized and used to investigate the extent and nature of this carbohydrate-arene interaction, as well as the effect on the overall 3D structure of the molecules involved. The sugar-aromatic distance was evaluated by rigorous NMR studies supported by molecular modeling and found to be constant throughout the series, independent of the nature of the sugar and of the conformational behavior of the fragment connecting the two elements. Ab initio calculations at the B3LYP/DZV(2d,p) level of theory enable the analysis of the electronic nature of the interaction. The study shows that, given the opportunity, persistent intramolecular aromatic-sugar interactions can be established and can significantly influence overall molecular shape and energetics. These results have important implications in the design of structural mimics of oligosaccharides.

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    • "The results show that ∼70% of bound monosaccharide units show an aromatic residue interacting with the carbohydrate aliphatic core, with Trp being the predominant (43% of the cases) followed by Tyr (33%) and Phe (24%). Overall these results are consistent with previous observations from our group and others (Asensio et al. 2000; Lütteke et al. 2005; Guardia et al. 2011), which show that lectins bind their ligands combining polar interactions with the ligand –OH group and an aromatic (nonpolar) interaction with the ligand aliphatic core (Guan et al. 2003; Sujatha et al. 2004; Terraneo et al. 2007; Laughrey et al. 2008; Nishio et al. 2014). "
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