title: 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.
abstract: We herein propose the use of fluoroacetamide and difluoroacetamide moieties as sensitive tags for the detection of sugar-protein interactions by simple1H and/or19F 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.
authors.affiliation: Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Bizkaia Technology Park, Building 801 A, 48170, Derio, Spain.
authors.forename: Luca
authors.initials: L
authors.lastname: Unione
authors.affiliation: Glycotechnology Laboratory, CICbiomaGUNE, Paseo Miramón, 20014, Donostia-San Sebastian, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Alcalá
authors.affiliation: Glycotechnology Laboratory, CICbiomaGUNE, Paseo Miramón, 20014, Donostia-San Sebastian, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Echeverria
authors.affiliation: Glycotechnology Laboratory, CICbiomaGUNE, Paseo Miramón, 20014, Donostia-San Sebastian, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Serna
authors.affiliation: Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Bizkaia Technology Park, Building 801 A, 48170, Derio, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ardá
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Profesor García González 1, 41012, Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Franconetti
authors.affiliation: Department of Chemical and Physical Biology, CIB-CSIC, Ramiro de Maeztu 9, 28040, Madrid, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.affiliation: Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Bizkaia Technology Park, Building 801 A, 48170, Derio, Spain.
authors.forename: Tammo
authors.initials: T
authors.lastname: Diercks
authors.affiliation: Glycotechnology Laboratory, CICbiomaGUNE, Paseo Miramón, 20014, Donostia-San Sebastian, Spain.|CIBER-BBN, Paseo Miramón, 20009, Donostia-San Sebastián, Spain.
authors.forename: Niels
authors.initials: N
authors.lastname: Reichardt
authors.affiliation: Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Bizkaia Technology Park, Building 801 A, 48170, Derio, Spain.|Basque Foundation for Science, Maria Diaz de Haro 13, 48009, Bilbao, Spain.|Department of Organic Chemistry II, Faculty of Science and Technology, University of the Basque Country, 48940, Leioa, Bizkaia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
mesh_terms: D004187:Disaccharides / Q000032:analysis / Q000378:metabolism*; D005463:Fluoroacetates / Q000032:analysis / Q000378:metabolism*; D054879:Halogenation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D046228:Microarray Analysis; D011485:Protein Binding; D014908:Triticum / Q000737:chemistry / Q000378:metabolism; D014909:Wheat Germ Agglutinins / Q000032:analysis / Q000378:metabolism*
chemical_list: D004187:Disaccharides; D005463:Fluoroacetates; D014909:Wheat Germ Agglutinins; C010913:N,N-diacetylchitobiose; C007741:fluoroacetamide
keywords: NMR spectroscopy; fluorine; molecular modeling; molecular recognition; noncovalent interactions