Molecular Recognition of Saccharides by Proteins. Insights on the Origin of the Carbohydrate−Aromatic Interactions

• Published in: Journal of the American Chemical Society 2005-05, Vol.127 (20), p.7379-7386
• Main Authors: Fernández-Alonso, María del Carmen, Cañada, Francisco Javier, Jiménez-Barbero, Jesús, Cuevas, Gabriel
• Format: Article
• Language: English
• Subjects: Benzene - chemistry; Biological and medical sciences; Carbohydrates - chemistry; Fundamental and applied biological sciences. Psychology; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Interactions. Associations; Intermolecular phenomena; Lectins - chemistry; Mannosides - chemistry; Methylgalactosides - chemistry; Methylmannosides; Models, Molecular; Molecular biophysics; Nuclear Magnetic Resonance, Biomolecular; Oligosaccharides - chemistry; Phenols - chemistry; Proteins - chemistry; Thermodynamics
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja051020+

The existence of stabilizing carbohydrate−aromatic interactions is demonstrated from both the theoretical and experimental viewpoints. The geometry of experimentally based galactose-lectin complexes has been properly accounted for by using a MP2/6-31G(d,p) level of theory and by considering a counterpoise correction during optimization. In this case, the stabilizing interaction energy of the fucose−benzene complex amounts to 3.0 kcal/mol. The theoretical results obtained herein indicate that the carbohydrate−aromatic interactions are stabilizing interactions with an important dispersive component and that electronic density between the sugar hydrogens and the aromatic ring indeed exists, thus giving rise to three so-called nonconventional hydrogen bonds. Experimental evidence of the intrinsic tendency of aromatic moieties to interact with certain sugars has also been shown by simple NMR experiments in water solution. Benzene and phenol specifically interact with the clusters of C−H bonds of the alpha face of methyl β-galactoside, without requiring the well-defined three-dimensional shape provided by a protein receptor, therefore resembling the molecular recognition features that are frequently observed in many carbohydrate−protein complexes.