Person: Canales Mayordomo, María Ángeles
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First Name
María Ángeles
Last Name
Canales Mayordomo
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Química Orgánica
Area
Química Orgánica
Identifiers
11 results
Search Results
Now showing 1 - 10 of 11
Item Revealing the Specificity of Human H1 Influenza A Viruses to Complex N-Glycans(JACS Au, 2023) Canales Mayordomo, María Ángeles; Sastre, Javier; Orduna, Jose M.; Spruit, Cindy M.; Perez-Castells, Javier; Dominguez, Gema; Bouwman, Kim M.; Van der Woude, Roosmarijn; Cañada, Francisco Javier; Nycholat, Corwin M.; Paulson, James C.; Boons, Geert-Jan; Jimenez-Barbero, Jesus; de Vries, Robert P.Influenza virus infection remains a threat to human health since viral hemagglutinins are constantly drifting, escaping infection and vaccine-induced antibody responses. Viral hemagglutinins from different viruses display variability in glycan recognition. In this context, recent H3N2 viruses have specificity for α2,6 sialylated branched N-glycans with at least three N-acetyllactosamine units (tri-LacNAc). In this work, we combined glycan arrays and tissue binding analyses with nuclear magnetic resonance experiments to characterize the glycan specificity of a family of H1 variants, including the one responsible for the 2009 pandemic outbreak. We also analyzed one engineered H6N1 mutant to understand if the preference for tri-LacNAc motifs could be a general trend in human-type receptor-adapted viruses. In addition, we developed a new NMR approach to perform competition experiments between glycans with similar compositions and different lengths. Our results point out that pandemic H1 viruses differ from previous seasonal H1 viruses by a strict preference for a minimum of di-LacNAc structural motifs.Item Molecular dynamics study of nanoconfined TIP4P/2005 water: how confinement and temperature affect diffusion and viscosity(Physical Chemistry Chemical Physics, 2019) Zaragoza, A.; González, Miguel A.; Joly, L.; López-Montero, Iván; Canales Mayordomo, María Ángeles; Benavides, A. L.; Valeriani, ChantalIn the past few decades great effort has been devoted to the study of water confined in hydrophobic geometries at the nanoscale (tubes and slit pores) due to the multiple technological applications of such systems, ranging from drug delivery to water desalination devices. To our knowledge, neither numerical/ theoretical nor experimental approaches have so far reached a consensual understanding of structural and transport properties of water under these conditions. In this work, we present molecular dynamics simulations of TIP4P/2005 water under different nanoconfinements (slit pores or nanotubes, with two degrees of hydrophobicity) within a wide temperature range. It has been found that water is more structured near the less hydrophobic walls, independently of the confining geometries. Meanwhile, we observe an enhanced diffusion coefficient of water in both hydrophobic nanotubes. Finally, we propose a confined Stokes–Einstein relation to obtain the viscosity from diffusivity, whose result strongly differs from the Green–Kubo expression that has been used in previous works. While viscosity computed with the Green–Kubo formula (applied for anisotropic and confined systems) strongly differs from that of the bulk, viscosity computed with the confined Stokes–Einstein relation is not so much affected by the confinement, independently of its geometry. We discuss the shortcomings of both approaches, which could explain this discrepancy.Item Competitive upconversion-linked immunoassay using peptide mimetics for the detection of the mycotoxin zearalenone(Biosensors and Bioelectronics, 2020) Peltomaa, Riikka Johanna; Farka, Zdeněk; Mickert, Matthias ; Brandmeier, Julian ; Pastucha, Matěj; Hlaváček, Antonín; Martínez Orts, Mónica; Canales Mayordomo, María Ángeles; Skládal, Petr; Benito Peña, María Elena; Moreno Bondi, María Cruz; Gorris, HansDue to increasing food safety standards, the analysis of mycotoxins has become essential in the food industry. In this work, we have developed a competitive upconversion-linked immunosorbent assay (ULISA) for the analysis of zearalenone (ZEA), one of the most frequently encountered mycotoxins in food worldwide. Instead of a toxin-conjugate conventionally used in competitive immunoassays, we designed a ZEA mimicking peptide extended by a biotin-linker and confirmed its excellent suitability to mimic ZEA by nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) analysis. Upconversion nanoparticles (UCNP, type NaYF4:Yb,Tm) served as background-free optical label for the detection of the peptide mimetic in the competitive ULISA. Streptavidin-conjugated UCNPs were prepared by click reaction using an alkyne-PEG-neridronate linker. The UCNP conjugate clearly outperformed conventional labels such as enzymes or fluorescent dyes. With a limit of detection of 20 pg mL−1 (63 pM), the competitive ULISA is well applicable to the detection of ZEA at the levels set by the European legislation. Moreover, the ULISA is specific for ZEA and its metabolites (α- and β-zearalenol) without significant cross-reactivity with other related mycotoxins. We detected ZEA in spiked and naturally contaminated maize samples using liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) as a reference method to demonstrate food analysis in real samples.Item Selective inhibition of cannabinoid CB1 receptor-evoked signalling by the interacting protein GAP43(Neuropharmacology, 2023) Maroto Martínez, Irene Berenice; Moreno, Estefanía; Costas Insúa, Carlos; Merino Gracia, Javier; Diez-Alarcia, Rebeca; Álvaro-Blázquez, Alicia; Canales Mayordomo, María Ángeles; Canela, Enric I.; Casadó, Vicent; Urigüen, Leyre; Rodríguez Crespo, José Ignacio; Guzmán Pastor, ManuelCannabinoids exert pleiotropic effects on the brain by engaging the cannabinoid CB1 receptor (CB1R), a presynaptic metabotropic receptor that regulates key neuronal functions in a highly context-dependent manner. We have previously shown that CB1R interacts with growth-associated protein of 43 kDa (GAP43) and that this interaction inhibits CB1R function on hippocampal excitatory synaptic transmission, thereby impairing the therapeutic effect of cannabinoids on epileptic seizures in vivo. However, the underlying molecular features of this interaction remain unexplored. Here, we conducted mechanistic experiments on HEK293T cells co-expressing CB1R and GAP43 and show that GAP43 modulates CB1R signalling in a strikingly selective manner. Specifically, GAP43 did not affect the archetypical agonist-evoked (i) CB1R/Gi/o protein-coupled signalling pathways, such as cAMP/PKA and ERK, or (ii) CB1R internalization and intracellular trafficking. In contrast, GAP43 blocked an alternative agonist-evoked CB1R-mediated activation of the cytoskeleton-associated ROCK signalling pathway, which relied on the GAP43-mediated impairment of CB1R/Gq/11 protein coupling. GAP43 also abrogated CB1R-mediated ROCK activation in mouse hippocampal neurons, and this process led in turn to a blockade of cannabinoid-evoked neurite collapse. An NMR-based characterization of the CB1R-GAP43 interaction supported that GAP43 binds directly and specifically through multiple amino acid stretches to the C-terminal domain of the receptor. Taken together, our findings unveil a CB1R-Gq/11-ROCK signalling axis that is selectively impaired by GAP43 and may ultimately control neurite outgrowth.Item Development of a Nucleotide Exchange Inhibitor That Impairs Ras Oncogenic Signaling(Chemistry: a european journal, 2017) Marín Ramos, Nagore Isasbel; Piñar Pinedo, María del Carmen; Vázquez Villa, Henar; Martín Fontecha, María del Mar; Gonzalez Wong, Ángel; Canales Mayordomo, María Ángeles; Algar Lizana, Sergio; Mayo Mariscal de Gante, Paloma P.; Jiménez-Barbero, Jesús; Gajate Fraile, Consuelo; Mollinedo García, Faustino; Pardo Carrasco, Leonardo; Ortega Gutiérrez, Silvia; Viso Beronda, Alma; López Rodríguez, María LuzDespite more than three decades of intense effort, no anti-Ras therapies have reached clinical application. Contributing to this failure has been an underestimation of Ras complexity and a dearth of structural information. In this regard, recent studies have revealed the highly dynamic character of the Ras surface and the existence of transient pockets suitable for small-molecule binding, opening up new possibilities for the development of Ras modulators. Herein, a novel Ras inhibitor (compound 12) is described that selectively impairs mutated Ras activity in a reversible manner without significantly affecting wild-type Ras, reduces the Ras–guanosine triphosphate (GTP) levels, inhibits the activation of the mitogen-activated protein kinase (MAPK) pathway, and exhibits remarkable cytotoxic activity in Ras-driven cellular models. The use of molecular dynamics simulations and NMR spectroscopy experiments has enabled the molecular bases responsible for the interactions between compound 12 and Ras protein to be explored. The new Ras inhibitor binds partially to the GTP-binding region and extends into the adjacent hydrophobic pocket delimited by switch II. Hence, Ras inhibitor 12 could represent a new compound for the development of more efficacious drugs to target Ras-driven cancers; a currently unmet clinical need.Item Análisis de las asociaciones de foraminíferos del Aaleniense en los márgenes oriental y noroccidental de la Placa Ibérica: implicaciones biogeográficas y bioestratigráficas(I Congresso Ibérico de Paleontologia: XVI Jornadas de la Sociedad Española de Paleontología, 2000) Canales Mayordomo, María Ángeles; Henriques, M.H.; Ureta Gil, María Soledad; Diez, J.B.; Balbino, A.C.Item Interactions between a Heparin Trisaccharide Library and FGF-1 Analyzed by NMR Methods(International Journal of Molecular Sciences, 2017) García-Jiménez, María José; Gil-Caballero, Sergio; Canales Mayordomo, María Ángeles; Jiménez-Barbero, Jesús; de Paz, José L.; Nieto, Pedro M.FGF-1 is a potent mitogen that, by interacting simultaneously with Heparan Sulfate Glycosaminoglycan HSGAG and the extracellular domains of its membrane receptor (FGFR), generates an intracellular signal that finally leads to cell division. The overall structure of the ternary complex Heparin:FGF-1:FGFR has been finally elucidated after some controversy and the interactions within the ternary complex have been deeply described. However, since the structure of the ternary complex was described, not much attention has been given to the molecular basis of the interaction between FGF-1 and the HSGAG. It is known that within the complex, the carbohydrate maintains the same helical structure of free heparin that leads to sulfate groups directed towards opposite directions along the molecular axis. The precise role of single individual interactions remains unclear, as sliding and/or rotating of the saccharide along the binding pocket are possibilities difficult to discard. The HSGAG binding pocket can be subdivided into two regions, the main one can accommodate a trisaccharide, while the other binds a disaccharide. We have studied and analyzed the interaction between FGF-1 and a library of trisaccharides by STD-NMR and selective longitudinal relaxation rates. The library of trisaccharides corresponds to the heparin backbone and it has been designed to interact with the main subsite of the protein.- Project number: 123
Item Operaciones básicas de laboratorio en el contexto de los objetivos de desarrollo sostenible (ODS)(2023) Ortega Gutiérrez, Silvia; Benhamú Salama, Bellinda; Canales Mayordomo, María Ángeles; Gámez Márquez, Francisco De Asis; Muñoz Oliva, Mª Riansares; Pérez Corona, Mª Teresa; Cilleros Prados, Olga; Sobrino Díaz, Mª Lourdes; Fernández Cabellos, Daniel; Sánchez Merino, AnabelEn este proyecto se pretende sensibilizar a los estudiantes en la importancia de los objetivos de desarrollo sostenible (ODS), fomentar su compromiso con los mismos y mostrar como la química puede contribuir de forma concreta y significativa a la consecución de los ODS. Item C60-based Multivalent Glycoporphyrins Inhibit SARS-CoV-2 Specific Interaction with the DC-SIGN Transmembrane Receptor(Small, 2023) Patino Alonso, Jennifer; Cabrera González, Justo Enrique; Merino Gracia, Javier; Nieta Ortiz, Gema; Katati, Jouma; Bezerra Da Cruz, Carlos; Mateos Gil, Pablo; Canales Mayordomo, María Ángeles; López Montero, Iván; Illescas Martínez, Beatriz María; Delgado Vázquez, Rafael; Martín León, NazarioSince WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry. Among others, C-type lectins such as DC-SIGN are identified as efficient trans-receptor for SARS-CoV-2 infection, so the use of glycomimetics to inhibit the infection through the DC-SIGN blockade is an encouraging approach. In this regard, multivalent nanostructures based on glycosylated [60]fullerenes linked to a central porphyrin scaffold have been designed and tested against DC-SIGN-mediated SARS-CoV-2 infection. First results show an outstanding inhibition of the trans-infection up to 90%. In addition, a deeper understanding of nanostructure-receptor binding is achieved through microscopy techniques, high-resolution NMR experiments, Quartz Crystal Microbalance experiments, and molecular dynamic simulations.Item Homogeneous immunoassay for cyclopiazonic acid based upon mimotopes and upconversion-resonance energy transfer(Biosensors and Bioelectronics, 2023) Prádanas González, Fernando; Peltomaa, Riikka Johanna; Lahtinen, Satu; Luque Uria, Álvaro; Más, Vicente ; Barderas, Rodrigo ; Maragos, Chris ; Canales Mayordomo, María Ángeles; Soukka, Terro; Benito Peña, María Elena; Moreno Bondi, María CruzStrains of Penicillium spp. are used for fungi-ripened cheeses and Aspergillus spp. routinely contaminate maize and other crops. Some of these strains can produce toxic secondary metabolites (mycotoxins), including the neurotoxin α-cyclopiazonic acid (CPA). In this work, we developed a homogeneous upconversion-resonance energy transfer (UC-RET) immunoassay for the detection of CPA using a novel epitope mimicking peptide, or mimotope, selected by phage display. CPA-specific antibody was used to isolate mimotopes from a cyclic 7-mer peptide library in consecutive selection rounds. Enrichment of antibody binding phages was achieved, and the analysis of individual phage clones revealed four different mimotope peptide sequences. The mimotope sequence, ACNWWDLTLC, performed best in phage-based immunoassays, surface plasmon resonance binding analyses, and UC-RET-based immunoassays. To develop a homogeneous assay, upconversion nanoparticles (UCNP, type NaYF4:Yb3+, Er3+) were used as energy donors and coated with streptavidin to anchor the synthetic biotinylated mimotope. Alexa Fluor 555, used as an energy acceptor, was conjugated to the anti-CPA antibody fragment. The homogeneous single-step immunoassay could detect CPA in just 5 min and enabled a limit of detection (LOD) of 30 pg/mL (1.5 μg/kg) and an IC50 value of 0.36 ng/mL. No significant cross-reactivity was observed with other co-produced mycotoxins. Finally, we applied the novel method for the detection of CPA in spiked maize samples using high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD) as a reference method.