Diastereomeric Glycosyl Sulfoxides Display Different Recognition Features versus E. coli β-Galactosidase

• Published in: European journal of organic chemistry 2016-10, Vol.2016 (30), p.5117-5122
• Main Authors: Colomer, Juan P., Fernández de Toro, Beatriz, Cañada, F. Javier, Corzana, Francisco, Jiménez Barbero, Jesús, Canales, Ángeles, Varela, Oscar
• Format: Article
• Language: English
• Subjects: Conformation analysis; Glycomimetics; Glycosidases; Molecular recognition
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201600835

The conformational analysis of the (S) and (R) diastereoisomers of benzyl 3‐deoxy‐4S‐(β‐d‐galactopyranosyl)‐4‐thio‐β‐d‐threo‐pentopyranoside S‐oxide (1S and 1R, respectively) has been performed by using NMR spectroscopy assisted by molecular modelling methods. The results point out that sulfoxide 1S and 1R display rather different conformational behaviors, 1S being significantly more flexible than 1R. Both sulfoxides have shown to be competitive inhibitors of the β‐galactosidase from E. coli, although with different potencies. The key structural features of the molecular recognition process have been characterized. The saccharide mimicry is an essential part of the development of sugar‐based drugs and/or molecular probes. In this work we characterize the conformational behavior of a glycosyl sulfoxide and its interaction with E. coli β‐galactosidase, by using NMR spectroscopy; (S) and (R) diastereroisomers of the sulfoxide could be analyzed, and each diastereomer displays a different potency as an enzyme inhibitor.