Seminar

Studies on the Molecular Recognition of aminoglycoside antibiotics by nucleic acids and proteins

Juan Luis Asensio, PhD

Carbohydrates are involved in a large variety of molecular recognition processes of biological relevance, involving both proteins and nucleic acid receptors. Understanding how these later bio-molecules interact with glycosides represents a fundamental issue in chemical biology with far reaching implications in fundamental biology, biotechnology or drug design. Aminoglycoside antibiotics constitute a paradigmatic example of biologically active glycosides. These compounds, widely used in clinics, bind to a large variety of RNA/DNA fragments, and, consequently, could be considered promising leads for the development of improved nucleic acid ligands. The description, in recent years, of several clinically relevant aminoglycoside/receptor complexes has greatly stimulated the structural-based design of new improved derivatives. Unfortunately, design efforts have frequently met a limited success, reflecting our incomplete understanding of the driving forces that promote complex formation. As a part of an ongoing project oriented to the study of carbohydrate molecular recognition in biological environments we have analyzed several key aspects of the aminoglycoside binding to RNA and proteins, employing a pluridisciplinar approach that includes NMR, molecular modeling, organic synthesis, and different biophysical techniques. The obtained results, together with alternative approaches for the design of improved aminoglycoside ligands, will be discussed. 1.-Jiménez-Moreno, E.; Montalvillo-Jiménez, L.; Santana, A.G.; Gómez, A.M.; Jiménez-Osés, G.; Corzana, F.; Bastida, A.; Jiménez-Barbero, J.; Cañada, F.J.; Gómez-Pinto, I.; González, C.; Asensio, J.L.* J. Am. Chem. Soc. 2016, 138, 20, 6463 2.-Jiménez-Moreno, E.; Jiménez-Osés, G.; Gómez, A.M. Santana, A.G.; Corzana, F.; Bastida, A.; Jiménez-Barbero, J.; Asensio, J.L.* Chemical Science 2015, 6, 6076. 3.-Jiménez-Moreno, E.; Gómez, A.M.; Bastida, A.; Corzana, F.; Jiménez-Oses, G.; Jiménez-Barbero, J.; Asensio, J.L. * Angew. Chem. Int. Edit. 2015, 54, 4344. 4.-Jiménez-Moreno, E.; Gómez-Pinto; I.; Corzana, F.; Santana, A.G.; Revuelta, J.; Bastida, A.; Jiménez-Barbero, J.; González, C.; Asensio, J.L.* Angew. Chem. Int. Edit. 2013, 52, 3148. 5.-Santana, A.G.; Jiménez-Moreno;, E.; Gómez, A.M.; Corzana, F.; González, C.; Jiménez-Oses, G.; Jiménez-Barbero, J.; Asensio, J.L.* J. Am. Chem. Soc. 2013, 135, 3347. 6.-Vacas, T.; Corzana, F.;Jimenez-Oses, G.; González, C.; Gomez, A.M.; Bastida, A.; Revuelta, J.; Asensio, J.L.* J. Am. Chem. Soc. 2010 132, 12074.