Effects of Sugar Functional Groups, Hydrophobicity, and Fluorination on Carbohydrate–DNA Stacking Interactions in Water

• Published in: Journal of organic chemistry Vol. 79; no. 6; pp. 2419 - 2429
• Main Authors: Lucas, Ricardo, Peñalver, Pablo, Gómez-Pinto, Irene, Vengut-Climent, Empar, Mtashobya, Lewis, Cousin, Jonathan, Maldonado, Olivia S, Perez, Violaine, Reynes, Virginie, Aviñó, Anna, Eritja, Ramón, González, Carlos, Linclau, Bruno, Morales, Juan C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21-03-2014
• Subjects: Base Pairing; Carbohydrates - chemistry; DNA - chemistry; Hydrocarbons, Fluorinated - chemistry; Hydrophobic and Hydrophilic Interactions; Magnetic Resonance Spectroscopy; Models, Molecular; Thermodynamics; Water - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo402700y

Carbohydrate–aromatic interactions are highly relevant for many biological processes. Nevertheless, experimental data in aqueous solution relating structure and energetics for sugar–arene stacking interactions are very scarce. Here, we evaluate how structural variations in a monosaccharide including carboxyl, N-acetyl, fluorine, and methyl groups affect stacking interactions with aromatic DNA bases. We find small differences on stacking interaction among the natural carbohydrates examined. The presence of fluorine atoms within the pyranose ring slightly increases the interaction with the C–G DNA base pair. Carbohydrate hydrophobicity is the most determinant factor. However, gradual increase in hydrophobicity of the carbohydrate does not translate directly into a steady growth in stacking interaction. The energetics correlates better with the amount of apolar surface buried upon sugar stacking on top of the aromatic DNA base pair.