Fluoroacetamide Moieties as NMR Spectroscopy Probes for the Molecular Recognition of GlcNAc‐Containing Sugars: Modulation of the CH–π Stacking Interactions by Different Fluorination Patterns

• Published in: Chemistry : a European journal Vol. 23; no. 16; pp. 3957 - 3965
• Main Authors: Unione, Luca, Alcalá, Maria, Echeverria, Begoña, Serna, Sonia, Ardá, Ana, Franconetti, Antonio, Cañada, F. Javier, Diercks, Tammo, Reichardt, Niels, Jiménez‐Barbero, Jesús
• Format: Journal Article
• Language: English
• Published: Germany John Wiley and Sons Inc 17.03.2017
• Subjects: Binders; Binding; Disaccharides - analysis; Disaccharides - metabolism; Fluorine; Fluoroacetates - analysis; Fluoroacetates - metabolism; Fragmentation; Halogenation; Magnetic Resonance Spectroscopy - methods; Microarray Analysis; Modulation; molecular modeling; molecular recognition; NMR spectroscopy; noncovalent interactions; Protein Binding; Recognition; Spectroscopy; Stacking; Triticum - chemistry; Triticum - metabolism; Wheat Germ Agglutinins - analysis; Wheat Germ Agglutinins - metabolism; molecular recognition; NMR spectroscopy; noncovalent interactions; molecular modeling; fluorine
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201605573

We herein propose the use of fluoroacetamide and difluoroacetamide moieties as sensitive tags for the detection of sugar–protein interactions by simple 1H and/or 19F NMR spectroscopy methods. In this process, we have chosen the binding of N,N′‐diacetyl chitobiose, a ubiquitous disaccharide fragment in glycoproteins, by wheat‐germ agglutinin (WGA), a model lectin. By using saturation‐transfer difference (STD)‐NMR spectroscopy, we experimentally demonstrate that, under solution conditions, the molecule that contained the CHF2CONH‐ moiety is the stronger aromatic binder, followed by the analogue with the CH2FCONH‐ group and the natural molecule (with the CH3CONH‐ fragment). In contrast, the molecule with the CF3CONH‐ isoster displayed the weakest intermolecular interaction (one order of magnitude weaker). Because sugar–aromatic CH–π interactions are at the origin of these observations, these results further contribute to the characterization and exploration of these forces and offer an opportunity to use them to unravel complex recognition processes. Push me, pull you: The fluorine‐induced polarization of the interacting CH in CFxHyCO‐ moieties with either one or two fluorine atoms provides an effective interaction point with proteins through CH–π stacking interactions (see figure).