Person: Martín-Fontecha Corrales, María Del Mar
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First Name
María Del Mar
Last Name
Martín-Fontecha Corrales
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Óptica y Optometría
Department
Química Orgánica
Area
Química Orgánica
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
Item Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery(Journal of Medicinal Chemistry, 2021) Huecas, Sonia; Araujo Bazán, Lidia; Ruiz, Federico M.; Ruiz Ávila, Laura, Laura B.; Martínez, R. Fernando; Escobar Peña, Ana Andrea; Artola, Marta; Vázquez Villa, María Del Henar; Martín-Fontecha Corrales, María Del Mar; Fernández Tornero, Carlos; López Rodríguez, María Luz; Andreu, José M.Bacterial resistance to antibiotics makes previously manageable infections again disabling and lethal, highlighting the need for new antibacterial strategies. In this regard, inhibition of the bacterial division process by targeting key protein FtsZ has been recognized as an attractive approach for discovering new antibiotics. Binding of small molecules to the cleft between the N-terminal guanosine triphosphate (GTP)-binding and the C-terminal subdomains allosterically impairs the FtsZ function, eventually inhibiting bacterial division. Nonetheless, the lack of appropriate chemical tools to develop a binding screen against this site has hampered the discovery of FtsZ antibacterial inhibitors. Herein, we describe the first competitive binding assay to identify FtsZ allosteric ligands interacting with the interdomain cleft, based on the use of specific high-affinity fluorescent probes. This novel assay, together with phenotypic profiling and X-ray crystallographic insights, enables the identification and characterization of FtsZ inhibitors of bacterial division aiming at the discovery of more effective antibacterials.- Project number: 243
Item eFACS: una plataforma para la realización de practicas de laboratorio virtuales de citometría de flujo(2021) Reche Gallardo, Pedro Antonio; Martin Villa, Jose Manuel; Lafuente Duarte, María Esther; Palomares Gracia, Oscar; Martín-Fontecha Corrales, María Del Mar; Cabañas Gutiérrez, Carlos; Aragón Pérez, Silvia; Peláez Prestel, Héctor Fernando; Sáchez-Trincado López, José Luis; Gómez Perosanz, Marta; Ras Carmona, Álvaro; Fiyouzi Alipour, Tara; Torres Gómez, ÁlvaroEn este proyecto hemos implementado un recurso online que permite simular el uso de un citómetro de Flujo de tres colores similar al FACScalibur. El citómetro de flujo es un instrumento esencial para la investigación básica y aplicada en biomedicina. Sin embargo, su uso requiere cierto entrenamiento y él análisis de muestras resulta costoso. Además, en universidades y hospitales no todos los departamentos disponen de un citómetro de flujo, usándose generalmente los disponibles en los centros de asistencia a la investigación. Como resultado los alumnos no tienen acceso a estos instrumentos y no tienen posibilidad de familiarizarse con las técnicas de citometría de flujo, recibiendo tan solo una información teórica sin llegar a saber hacer. En este contexto, la herramienta eFACS : • Soluciona la falta de accesibilidad y disponibilidad de citómetro de flujo para uso del estudiante • Posibilita la generación de material didáctico que permita al alumno planear y ejecutar un experimento de citometría de flujo y que aprendan haciendo. • Posibilita el entrenamiento de los usuarios en un simulador antes de enfrentarse a un citómetro de flujo real. El recurso eFACS es en conclusión un gran apoyo tanto para la docencia como para la investigación. Item The Search for Antibacterial Inhibitors Targeting Cell Division Protein FtsZ at Its Nucleotide and Allosteric Binding Sites.(Biomedicines, 2022) Andreu Rodríguez, José Manuel; Huecas Gayo, Sonia; Araujo Bazán, Lidia; Vázquez Villa, Henar; Martín-Fontecha Corrales, María Del MarThe global spread of bacterial antimicrobial resistance is associated to millions of deaths from bacterial infections per year, many of which were previously treatable. This, combined with slow antibiotic deployment, has created an urgent need for developing new antibiotics. A still clinically unexploited mode of action consists in suppressing bacterial cell division. FtsZ, an assembling GTPase, is the key protein organizing division in most bacteria and an attractive target for antibiotic discovery. Nevertheless, developing effective antibacterial inhibitors targeting FtsZ has proven challenging. Here we review our decade-long multidisciplinary research on small molecule inhibitors of bacterial division, in the context of global efforts to discover FtsZ-targeting antibiotics. We focus on methods to characterize synthetic inhibitors that either replace bound GTP from the FtsZ nucleotide binding pocket conserved across diverse bacteria or selectively bind into the allosteric site at the interdomain cleft of FtsZ from Bacillus subtilis and the pathogen Staphylococcus aureus. These approaches include phenotype screening combined with fluorescence polarization screens for ligands binding into each site, followed by detailed cytological profiling, and biochemical and structural studies. The results are analyzed to design an optimized workflow to identify effective FtsZ inhibitors, and new approaches for the discovery of FtsZ-targeting antibiotics are discussed.Item Chemoproteomic Approach to Explore the Target Profile of GPCR ligands: Application to 5-HT1A and 5-HT6 Receptors(Chemistry a European Journal, 2015) Gamo, Ana M.; Gónzalez-Vera, Juan A.; Rueda-Zubiaurre, Ainoa; Alonso, Dulce; Vázquez-Villa, Henar; Martín-Couce, Lidia; Palomares, Oscar; López, Juan A.; Martín-Fontecha Corrales, María Del Mar; Benhamú, Bellinda; López-Rodríguez, María L.; Ortega-Gutiérrez, SilviaDetermination of the targets of a compound remains an essential aspect in drug discovery. A complete understanding of all binding interactions is critical to recognize in advance both therapeutic effects and undesired consequences. However, the complete polypharmacology of many drugs currently in clinical development is still unknown, especially in the case of G-protein-coupled receptor (GPCR) ligands. In this work we have developed a chemoproteomic platform based on the use of chemical probes to explore the target profile of a compound in biological systems. As proof of concept, this methodology has been applied to selected ligands of the therapeutically relevant serotonin 5-HT1A and 5-HT6 receptors, and we have identified and validated some of their off-targets. This approach could be extended to other drugs of interest to study the targeted proteome in disease-relevant systems.- Project number: 77
Item Adaptación de las prácticas de laboratorio de Materiales en Óptica Oftálmica y Lentes de contacto a metodologías de aprendizaje activo basado en la experimentación(2023) Orden Hernández, María Ulagares De La; Escobar Peña, Ana Andrea; Jiménez García, Inmaculada; Lasagabaster Latorre, Aurora; Macicior Michelena, Jon; Martín-Fontecha Corrales, María Del Mar; Molina Santos, Marina Mercedes; Marinov, Lyuboslav Nikolaev; Ortiz García, María Josefa; Rodríguez Agarrabeitia, AntoniaEste proyecto pretende rediseñar las prácticas de Materiales Ópticos y adaptarlas a los principios del Aprendizaje Activo Basado en la Experimentación (ABE) implementando herramientas de Aula Invertida y Aprendizaje Cooperativo Item Isoprenylcysteine Carboxylmethyltransferase-Based Therapy for Hutchinson−Gilford Progeria Syndrome(ACS Central Science, 2021) Marcos Ramiro, Beatriz; Gil Ordóñez, Ana; Marín Ramos, Nagore I.; Ortega Nogales, Francisco J.; Balabasquer, Moisés; Gonzalo, Pilar; Ortega Gutiérrez, Silvia; Khiar Fernández, Nora; Rolas, Loic; Barkaway, Anna; Nourshargh, Sussan; Andrés, Vicente; Martín-Fontecha Corrales, María Del Mar; López Rodríguez, María LuzHutchinson–Gilford progeria syndrome (HGPS, progeria) is a rare genetic disease characterized by premature aging and death in childhood for which there were no approved drugs for its treatment until last November, when lonafarnib obtained long-sought FDA approval. However, the benefits of lonafarnib in patients are limited, highlighting the need for new therapeutic strategies. Here, we validate the enzyme isoprenylcysteine carboxylmethyltransferase (ICMT) as a new therapeutic target for progeria with the development of a new series of potent inhibitors of this enzyme that exhibit an excellent antiprogeroid profile. Among them, compound UCM-13207 significantly improved the main hallmarks of progeria. Specifically, treatment of fibroblasts from progeroid mice with UCM-13207 delocalized progerin from the nuclear membrane, diminished its total protein levels, resulting in decreased DNA damage, and increased cellular viability. Importantly, these effects were also observed in patient-derived cells. Using the LmnaG609G/G609G progeroid mouse model, UCM-13207 showed an excellent in vivo efficacy by increasing body weight, enhancing grip strength, extending lifespan by 20%, and decreasing tissue senescence in multiple organs. Furthermore, UCM-13207 treatment led to an improvement of key cardiovascular hallmarks such as reduced progerin levels in aortic and endocardial tissue and increased number of vascular smooth muscle cells (VSMCs). The beneficial effects go well beyond the effects induced by other therapeutic strategies previously reported in the field, thus supporting the use of UCM-13207 as a new treatment for progeria.