The Nuclear Magnetic Resonance and Molecular Recognition (NMRMR) group is interested, from a general point of view, in the study of molecular recognition processes with special emphasis on carbohydrate-receptor interactions applying and developing methodologies based on NMR with the main objective of characterizing the structure and dynamics of carbohydrates, proteins, their complexes and, in general, of other biomolecules in solution. The achievement of this objective will allow from one side the understanding at atomic scale the participation and importance of carbohydrates in essential biological processes and on the other side will facilitate the design of new molecules and/or analogues of carbohydrates in order to modulate those processes.
The NMRMR group follows a multidisciplinary approach, beyond its specialization in the use and development of methodologies based on NMR, which covers organic synthesis, molecular biology and computational chemistry within a collaborative strategy with other research groups either at CIB or from other national and international research institutions.
The NMRMR group is conducting studies on the interactions of carbohydrates with different types of receptors: lectins and receptors of the immunological system, viral hemagglutinins and receptors, plant lectins, glycosidase enzymes and antibodies. In this context, the group is carrying out a collaborative project with the company Inmunotek with the objective of developing antineoplastic or anti-allergic vaccines that incorporate carbohydrates
On the other hand, the NMR strategies developed by the group, either from the point of view of the receptor or the ligand, are been extended to the study of other biological systems also in collaboration with other groups at CIB and external .
Y. Shen, I. Kalograiaki, A. Prunotto, M. Dunne, S. Boulos, N. M. I. Taylor, E. T. Sumrall, M. R. Eugster, R. Martin, A. Julian-Rodero, B. Gerber, P. G. Leiman, M. Menéndez, M. D. Peraro, F. J. Cañada & M. J. Loessner . Structural basis for recognition of bacterial cell wall teichoic acid by pseudo-symmetric sh3b-like repeats of a viral peptidoglycan hydrolase. Chemical Science. doi: 10.1039/D0SC04394J
A. G. Santana, L. Montalvillo-Jimenez, L. Diaz-Casado, F. Corzana, P. Merino, F. J. Cañada, G. Jiménez-Oses, J. Jiménez-Barbero, A. M. Gómez & J. L. Asensio . Dissecting the essential role of anomeric beta-triflates in glycosylation reactions. J. Am. Chem. Soc., 142(28), 12501-12514. doi: 10.1021/jacs.0c05525
M. A. Pajares, T. Zimmermann, F. J. Sanchez-Gomez, A. Ariza, M. J. Torres, M. Blanca, F. J. Cañada, M. I. Montañez & D. Perez-Sala . Amoxicillin inactivation by thiol-catalyzed cyclization reduces protein haptenation and antibacterial potency. Front. Pharmacol., 11 doi: 10.3389/fphar.2020.00189
M. Nieto-Domínguez, B. Fernández De Toro, L. I. De Eugenio, A. G. Santana, L. Bejarano-Muñoz, Z. Armstrong, J. A. Méndez-Líter, J. L. Asensio, A. Prieto, S. G. Withers, F. J. Cañada & M. J. Martínez . Thioglycoligase derived from fungal gh3 β-xylosidase is a multi-glycoligase with broad acceptor tolerance. Nature Communications, 11(1), 4864. doi: 10.1038/s41467-020-18667-3
A. Gimeno, S. Delgado, P. Valverde, S. Bertuzzi, M. A. Berbis, J. Echavarren, A. Lacetera, S. Martin-Santamaria, A. Surolia, F. J. Cañada, J. Jimenez-Barbero & A. Arda . Minimizing the entropy penalty for ligand binding: Lessons from the molecular recognition of the histo blood-group antigens by human galectin-3. Angew. Chem.-Int. Edit., 58(22), 7268-7272. doi: 10.1002/anie.201900723
Canal-Martín, Andrea, Sastre, Javier, Sánchez-Barrena, María José, Canales, Angeles, Baldominos, Sara, Pascual, Naiara, Martínez-González, Loreto, Molero, Dolores, Fernández-Valle, Mª Encarnación, Sáez, Elena, Blanco-Gabella, Patricia, Gómez-Rubio, Elena, Martín-Santamaría, Sonsoles, Sáiz, Almudena, Mansilla, Alicia, Cañada, F. Javier, Jiménez-Barbero, Jesús, Martínez, Ana, Pérez-Fernández, Ruth . Insights into real-time chemical processes in a calcium sensor protein-directed dynamic library. Nature Communications. 10:2798
Ayuso-Fernandez, I., De Lacey, A. L., Canada, F. J., Ruiz-Duenas, F. J., Martinez, A. T. . Increase of Redox Potential during the Evolution of Enzymes Degrading Recalcitrant Lignin. Chemistry-a European Journal. 25:2708-2712 doi: 10.1002/chem.201805679
Fernández de Toro, B., Peng, W., Thompson, A.J., Domínguez, G., Cañada, F.J., Pérez-Castells, J., Paulson, J.C., Jiménez-Barbero, J., Canales, Á. . Avenues to Characterize the Interactions of Extended N-Glycans with Proteins by NMR Spectroscopy: The Influenza Hemagglutinin Case. Angewandte Chemie - International Edition. 57:15051-15055.
Espaillat, A., Forsmo, O., El Biari, K., Björk, R., Lemaitre, B., Trygg, J., Cañada, F.J., De Pedro, M.A., Cava, F. . Chemometric Analysis of Bacterial Peptidoglycan Reveals Atypical Modifications That Empower the Cell Wall against Predatory Enzymes and Fly Innate Immunity. Journal of the American Chemical Society. 138:9193-9204.
Sirvent, S., Soria, I., Cirauqui, C., Cases, B., Manzano, A.I., Diez-Rivero, C.M., Reche, P.A., López-Relaño, J., Martínez-Naves, E., Cañada, F.J., Jiménez-Barbero, J., Subiza, J., Casanovas, M., Fernández-Caldas, E., Subiza, J.L., Palomares, O. . Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1. Journal of Allergy and Clinical Immunology. 138:558-567.
Comunity of Madrid. Biomedicine , S2017/BMD-3673 (2018-2021)
Isolation, purification and structural elucidation of carbohydrate-nature tumoral marker Ca10 defined by the monoclonal antibody A10
Inmunotek S.L. (2017-2020)
NMR and Molecular Recognition of Carbohydrates : Lectins, Enzymes and Nucleic Acids .
MICINN, RTI2018-094751-B-C2-P2 (2019-2021)
New antineoplasic vaccine based in the tumoral carbohydrate Ca10
MINECO, RETOS COLABORACIÓN, RTC-2015-3805-1 (2015-2019)
Coordinator: Inmunotek S.L.
During last years, we have contributed to the study of diverse molecular recognition processes of sugars by lectins, enzymes, antibodies and nucleic acids. We have pioneered the use of trNOE to deduce the bioactive conformation of saccharides and glycomimetics and the employment of STD experiments to validate the ligand epitope. We have developed and applied NMR strategies based on fluorine observation using synthetic fluorinated glycomimetics. The introduction of paramagnetic tags has allow us to resolve and observe independently pseudosymmetric components in oligosaccharides otherwise unresolvable. Also we have shown the importance of CH-pi interactions for sugar recognition by receptors.
We apply and develop NMR strategies to study molecular recognition processes based on chemical shift perturbation (CSP), saturation transfer difference (STD), transferred nuclear Overhausser effect (TR-NOE), diffusion coefficient-based strategies (DOSY Diffusion Ordered Spectroscopy), relaxation perturbation (T2 filters) and paramagentic perturbations (pseudo contact shifts). When possible, the characterization the three-dimensional structures of the receptors and their complexes in solution is pursued at atomic level by NMR approaches complemented with molecular modelling and computational calculations. Apart of NMR, the team has also access to other techniques, which may allow deducing other physicochemical and thermodymic parameters parameters relevant to the study of intermolecular interactions.
Our expertise in NMR methodologies to study molecular recognition allow us to establish national and international collaborations and also actively collaborate with several groups at CIB in common financed projects (Complement-II with Molecular Pathology/ Complement Genetics, Structural Biology of Host-Pathogen Interactions and Computational Chemical Biology) and recent joint publications (with groups Biotechnology for Lignocellulosic Biomass, Posttranslational modification of proteins, Translational Medicinal and Biological Chemistry, Environmental Microbiology) and some other studies in course.
Prof F. Javier Cañada (PhD in Chemistry) is full Professor from CSIC from 2007. He has published more than 200 publications and has delivered a variety of lectures at national and international meetings and Institutions. He has supervised 13 PhD Thesis and 2 in course. His expertise is in the molecular recognition, NMR, carbohydrates chemistry and biochemistry, chemical biology and molecular biology fields.