Protein-Carbohydrate Interactions Studied by NMR: From Molecular Recognition to Drug Design

Maria      del Carmen Fernandez-Alonso; Dolores      Diaz; Manuel      Alvaro Berbis; Filipa      Marcelo; Javier      Canada; Jesus      Jimenez-Barbero

Abstract

Diseases that result from infection are, in general, a consequence of specific interactions between a pathogenic organism and the cells. The study of host-pathogen interactions has provided insights for the design of drugs with therapeutic properties. One area that has proved to be promising for such studies is the constituted by carbohydrates which participate in biological processes of paramount importance. On the one hand, carbohydrates have shown to be information carriers with similar, if not higher, importance than traditionally considered carriers as amino acids and nucleic acids. On the other hand, the knowledge on molecular recognition of sugars by lectins and other carbohydrate-binding proteins has been employed for the development of new biomedical strategies. Biophysical techniques such as X-Ray crystallography and NMR spectroscopy lead currently the investigation on this field. In this review, a description of traditional and novel NMR methodologies employed in the study of sugar-protein interactions is briefly presented in combination with a palette of NMR-based studies related to biologically and/or pharmaceutically relevant applications.

Keywords: NMR, molecular modeling, protein-ligand interactions, drug targeting, Carbohydrate-Protein Interaction, Apolar Interactions, Hydrogen Bonding, PROTEIN-CARBOHYDRATE INTERACTIONS, Distortion of Sugar Rings, Isotope Labeling