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Francisco Javier Cañada

Francisco Javier Cañada
Centro de Investigaciones Biológicas Margarita Salas Spanish National Research Council

PhD

About

267
Publications
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10,511
Citations
Additional affiliations
October 2002 - present
Margarita Salas Center for Biological Research
Position
  • Professor (Full)

Publications

Publications (267)
Article
Hemagglutinins (HAs) from human influenza viruses descend from avian progenitors that bind α2–3-linked sialosides, and must adapt to glycans with α2–6-linked sialic acids on human airway cells to transmit within the human population. Since their introduction during the 1968 pandemic, H3N2 viruses have evolved over the past five decades to preferent...
Article
Full-text available
Functional Tregs play a key role in tumor development and progression, representing a major barrier to anticancer immunity. The mechanisms by which Tregs are generated in cancer and the influence of the tumor microenvironment on these processes remain incompletely understood. Herein, by using NMR, chemoenzymatic structural assays and a plethora of...
Article
Full-text available
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...
Article
Full-text available
Resveratrol is a natural polyphenol with antioxidant activity and numerous health benefits. However, in vivo application of this compound is still a challenge due to its poor aqueous solubility and rapid metabolism, which leads to an extremely low bioavailability in the target tissues. In this work, rXynSOS-E236G glycosynthase, designed from a GH10...
Preprint
Full-text available
Influenza virus infection remains a threat to human health since viral hemagglutinins are constantly drifting, escaping infec-tion and vaccine-induced antibody responses. During antigenic drift H3 hemagglutinins have evolved to recognize a2,6 sialylated branched N-glycans with long glycan chains with at least three N-acetyllactosamine units (tri-La...
Poster
Full-text available
Factor H (FH) is the main regulator of the alternative pathway (AP) both in fluid phase and on cell surfaces. The ability to regulate complement on cell surfaces relies on the capacity of the C-terminus of FH to simultaneously interact with deposited C3b and 2,3´sialic acid. We have recently described that factor H-related protein 1 (FHR-1) does no...
Article
Full-text available
The study of endoxylanases as catalysts to valorize hemicellulosic residues and to obtain glycosides with improved properties is a topic of great industrial interest. In this work, a GH10 β-1,4-endoxylanase (XynSOS), from the ascomycetous fungus Talaromyces amestolkiae, has been heterologously produced in Pichia pastoris, purified, and characterize...
Article
Carbohydrates, either free or as glycans conjugated with other biomolecules, participate in many essential biological processes. Their apparent simplicity in terms of chemical functionality hides an extraordinary diversity and structural complexity. Deeply deciphering at the atomic level their structures is essential to understand their biological...
Article
Full-text available
The tandem-repeat Galectin-4 (Gal-4) contains two different domains covalently linked through a short flexible peptide. Both domains have been shown to bind preferentially to A and B histo blood group antigens with different affinities, although the binding details are not yet available. The biological relevance of these associations is unknown, al...
Article
Full-text available
The human macrophage galactose lectin (MGL) is an endocytic type II transmembrane receptor expressed on immature monocyte-derived dendritic cells and activated macrophages and plays a role in modulating the immune system in response to infections and cancer. MGL contains an extracellular calcium-dependent (C-type) carbohydrate recognition domain (C...
Article
Full-text available
Factor H-related proteins (FHRs) are a group of partly characterized complement proteins that are thought to promote complement activation by competing binding of factor H (FH) to surface-bound C3b. Among them, FHR-1 is remarkable because is associated with atypical hemolytic uremic syndrome (aHUS) and other important diseases. Using a combination...
Article
Full-text available
Cyclopropanated iminosugars have a locked conformation that may enhance the inhibitory activity and selectivity against different glycosidases. We show the synthesis of new cyclopropane-containing piperidines bearing five stereogenic centers from natural amino acids l-serine and l-alanine. Those prepared from the latter amino acid may mimic l-fucos...
Article
Full-text available
Synthesis of four iminosugars fused to a cyclopropane ring is described using l-serine as the chiral pool. The key steps are large-scale preparation of an α,β-unsaturated piperidinone followed by completely stereoselective sulfur ylide cyclopropanation. Stereochemistry of compounds has been studied by nuclear Overhauser effect spectroscopy (NOESY)...
Article
Full-text available
Molecular recognition of carbohydrates is a key step in essential biological processes. Carbohydrate receptors can distinguish monosaccharides even if they only differ in a single aspect of the orientation of the hydroxyl groups or harbor subtle chemical modifications. Hydroxyl-by-fluorine substitution has proven its merits for chemically mapping t...
Article
Full-text available
Calix[4]arene PTX008 is an angiostatic agent that inhibits tumor growth in mice by binding to galectin‐1, a β‐galactoside‐binding lectin. To assess the affinity profile of PTX008 for galectins, we used ¹⁵N,¹H HSQC NMR spectroscopy to show that PTX008 also binds to galectin‐3 (Gal‐3), albeit more weakly. We identified the contact site for PTX008 on...
Article
Full-text available
Endolysins are bacteriophage-encoded peptidoglycan hydrolases targeting the cell wall of host bacteria via their cell wall-binding domains (CBDs). The molecular basis for selective recognition of surface carbohydrate ligands by CBDs remains elusive. Here, we describe, in atomic detail, the interaction between the Listeria phage endolysin domain CBD...
Article
Full-text available
The synthesis of customized glycoconjugates constitutes a major goal for biocatalysis. To this end, engineered glycosidases have received great attention and, among them, thioglycoligases have proved useful to connect carbohydrates to non-sugar acceptors. However, hitherto the scope of these biocatalysts was considered limited to strong nucleophili...
Chapter
This chapter is dedicated to the presentation of different examples of the application of solution NMR to the study of conformation, dynamics of sugar molecules (oligo and polysaccharides, glycopeptides and glycomimetics) including the investigation of glycan-related molecular recognition events. It is not our intention to be exhaustive, rather to...
Article
Full-text available
Fluorinated glycomimetics are frequently employed to study and eventually modulate protein–glycan interactions. However, complex glycans and their glycomimetics may display multiple binding epitopes that enormously complicate the access to a complete picture of the protein–ligand complexes. We herein present a new methodology based on the synergic...
Article
Full-text available
Carbohydrates play a pivotal role in intercellular communication processes. In particular, glycan antigens are key for sustaining homeostasis, helping leukocytes to distinguish damaged tissues and invading pathogens from healthy tissues. From a structural perspective, this cross‐talk is fairly complex, and multiple membrane proteins guide these rec...
Article
Glycosylations promoted by triflate-generating reagents are widespread synthetic methods for the construction of glycosidic scaffolds and glycoconjugates of biological and chemical interest. These processes are thought to proceed with the participation of a plethora of activated high energy intermediates such as the α- and β-glycosyl triflates, or...
Article
Full-text available
Background: The interest for finding novel β-glucosidases that can improve the yields to produce second-generation (2G) biofuels is still very high. One of the most desired features for these enzymes is glucose tolerance, which enables their optimal activity under high-glucose concentrations. Besides, there is an additional focus of attention on f...
Preprint
Endolysins are bacteriophage-encoded peptidoglycan hydrolases targeting the cell wall of host bacteria via their cell wall-binding domains (CBDs). The molecular basis for selective recognition of surface carbohydrate ligands by CBDs remains elusive. Here, we describe, in atomic detail, the interaction between the Listeria phage endolysin domain CBD...
Article
Full-text available
Serum and cellular proteins are targets for the formation of adducts with the β-lactam antibiotic amoxicillin. This process could be important for the development of adverse, and in particular, allergic reactions to this antibiotic. In studies exploring protein haptenation by amoxicillin, we observed that reducing agents influenced the extent of am...
Preprint
Full-text available
Background: The interest for finding novel b-glucosidases that can improve the yields to produce second-generation (2G) biofuels is still very high. One of the most desired features for these enzymes is glucose tolerance, which enables their optimal activity under high-glucose concentrations. Besides, there is an additional focus of attention on fi...
Article
Full-text available
Background: Currently, industrial societies are seeking for green alternatives to conventional chemical synthesis. This demand has merged with the efforts to convert lignocellulosic biomass into value-added products. In this context, xylan, as one of main components of lignocellulose, has emerged as a raw material with high potential for advancing...
Article
Full-text available
Background: 5-Hydroxymethylfurfural (HMF) is a highly valuable platform chemical that can be obtained from plant biomass carbohydrates. HMF can be oxidized to 2,5-furandicarboxylic acid (FDCA), which is used as a renewable substitute for the petroleum-based terephthalic acid in polymer production. Results: Aryl-alcohol oxidase (AAO) from the whi...
Article
An unprecedented approach towards oligosaccharides containing N-acetylglucosamine-N-acetylmuramic (NAG-NAM) units was developed. These novel bacterial cell wall surrogates were obtained from chitosan via a top down approach involving both chemical and enzymatic reactions. The chemical modification of chitosan using a molecular clamp based strategy,...
Article
Full-text available
Dynamic combinatorial chemistry (DCC) has proven its potential in drug discovery speeding the identification of modulators of biological targets. However, the exchange chemistries typically take place under specific reaction conditions, with limited tools capable of operating under physiological parameters. Here we report a catalyzed protein-direct...
Article
Full-text available
A fluorine nuclear magnetic resonance (19F-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of biomedical interest, which is involved in different vi...
Article
Full-text available
The dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an important recep-tor of the immune system. Besides its role as pathogen recognition receptor (PRR), it also interacts with endogenous glycoproteins through the specific recognition of self-glycan epitopes, like Lex. This lectin however, represents a p...
Article
Full-text available
Background: Transglycosylation represents one of the most promising approaches for obtaining novel glycosides, and plant phenols and polyphenols are emerging as one of the best targets for creating new molecules with enhanced capacities. These compounds can be found in diet and exhibit a wide range of bioactivities, such as antioxidant, antihypert...
Article
Full-text available
Wheat germ agglutinin (WGA) is a lectin composed of 4 homologous hevein domains. It has been shown that WGA binds N-acetyl glucosamine (GlcNAc)-related oligosaccharides and has applications as commercial reagent to detect glycans containing such modified residues. Peptidoglycan (PGN), the main component of the bacterial cell wall, is a polymeric ma...
Preprint
Full-text available
Serum and cellular proteins are targets for the formation of adducts with the β-lactam antibiotic amoxicillin. This process could be important for the development of adverse, and in particular, allergic reactions to this antibiotic. In studies exploring protein haptenation by amoxicillin, we observed that reducing agents influenced the extent of am...
Article
Full-text available
Ligand conformational entropy plays an important role in carbohydrate recognition events. Glycans are characterized by intrinsic flexibility around the glycosidic linkages, thus in most cases, loss of conformational entropy of the sugar upon complex formation strongly affects the entropy of the binding process. By employing a multidisciplinary appr...
Article
Full-text available
The cell membrane regulates the exchange of molecules and information with the external environment. However, this control barrier hinders the delivery of exogenous bioactive molecules that can be applied to correct cellular malfunctions. Therefore, the traffic of macromolecules across the cell membrane represents a great challenge for the developm...
Article
Full-text available
Two-component signal transduction systems comprise a sensor histidine kinase and its cognate response regulator, and some have evolved to sense and convert redox signals into regulatory outputs that allow bacteria to adapt to the altered redox environment. The work presented here expands knowledge of the functional diversity of redox-sensing kinase...
Article
Ligand conformational entropy is generally claimed as an important contribution in carbohydrate recognition events. Indeed, glycans are characterized by an intrinsic flexibility around the glycosidic linkages, and thus, except for isolated cases, the loss of conformational entropy of the sugar upon complex formation strongly impacts the entropy of...
Article
Full-text available
To investigate how ligninolytic peroxidases acquired the uniquely high redox potential they show today, their ancestors were resurrected and characterized. Unfortunately, the transient Compounds I (CI) and II (CII) from peroxide activation of the enzyme resting state (RS) are unstable. Therefore, the reduction potentials (E°′) of the three redox co...
Article
Full-text available
Bacterial surfaces are decorated with carbohydrate structures that may serve as ligands for host receptors. Based on their ability to recognize specific sugar epitopes, plant lectins are extensively used for bacteria typing. We previously observed that the galactose-specific agglutinins from Ricinus communis (RCA) and Viscum album (VAA) exhibited d...
Article
Murine adenovirus 2 (MAdV-2) infects cells of the mouse gastrointestinal tract. Like human adenoviruses, it is a member of the genus Mastadenovirus, family Adenoviridae. The MAdV-2 genome has a single fibre gene that expresses a 787 residue-long protein. Through analogy to other adenovirus fibre proteins, it is expected that the carboxy-terminal vi...
Article
Full-text available
Long chain multiantenna N‐glycans are extremely complex molecules from the structural perspective. Their inherent flexibility and the presence of repetitions of monosaccharide units in similar chemical environments hamper their full characterization by X‐ray diffraction or standard NMR methodologies. Therefore, the exploration of their interaction...
Article
Full-text available
Long chain multiantenna N‐glycans are extremely complex molecules from the structural perspective. Their inherent flexibility and the presence of repetitions of monosaccharide units in similar chemical environments hamper their full characterization by X‐ray diffraction or standard NMR methodologies. Therefore, the exploration of their interaction...
Article
Protein-protein interactions (PPI) are known to play an essential role between the neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor Ric8a to regulate synapse function, emerging as a druggable interface for synaptopathies such as the Fragile X syndrome (FXS). Recently, the phenothiazine FD44 has been identified as an inhibitor of th...
Article
Targeting carbohydrate recognition plays a key role in multiple biological processes across all kingdoms. SH3b (or bacterial Src homology 3) domain is known as a conserved carbohydrate‐binding module that is responsible for carbohydrate recognition. However, the molecular and structural mechanisms underlying SH3b‐carborhydrate interaction remain el...
Article
Seasonal flu (influenza virus infection) is one of the major threats to human health, causing of up to 500 thousands deaths worldwide annually.1,2 Hemagglutinin, a glycoprotein presented in the surface of the influenza virus, binds sialylated N‐glycans located on the surface of host epithelial cells. The structural elucidation and the conformationa...
Article
N‐glycans are ubiquitous in nature and functionalize glycoproteins. Protein glycosylation is required for proper biological and biophysical function and often, alterations in glycosylation are related to diseases.[1] Complex glycosylation patterns containing multiantennary N‐glycans are typically found in mature glycoproteins. However, the structur...
Article
Alzheimer's disease (AD) is the most common form of dementia worldwide with an increasing prevalence for the next years. The multifactorial nature of AD precludes the design of new drugs directed to a single target being probably one of the reasons for recent failures. Therefore, dual binding site acetylcholinesterase (AChE) inhibitors have been re...
Article
Full-text available
The biological recognition of complex-type N-glycans is part of many key physiological and pathological events. Despite their importance, the structural characterization of these events remains an unsolved task. The inherent flexibility of N-glycans hampers crystallization and the chemical equivalence of individual branches precludes their NMR char...
Article
Full-text available
The biological recognition of complex-type N-glycans is part of many key physiological and pathological events. Despite their importance, the structural characterization of these events remains an unsolved task. The inherent flexibility of N-glycans hampers crystallization and the chemical equivalence of individual branches precludes their NMR char...
Article
The lack of an effective treatment for Alzheimer' disease (AD), an increasing prevalence and severe neurodegenerative pathology, boost medicinal chemists to look for new drugs. Currently, only acethylcholinesterase (AChE) inhibitors and glutamate antagonist have been approved to the palliative treatment of AD. Although they have a short-term sympto...
Article
Full-text available
We have recently reported that grass pollen allergoids conjugated with non oxidized mannan of Saccharomyces cerevisae using glutaraldehyde results in a novel hypoallergenic mannan-allergen complex with improved properties for allergen vaccination. Using this approach, human dendritic cells show a better allergen uptake and cytokine profile producti...
Article
Glycans play a key role as recognition elements in the communication of cells and other organisms. Thus, the analysis of carbohydrate-protein interactions has gained significant importance. In particular, Nuclear Magnetic Resonance (NMR) techniques are considered powerful tools to detect relevant features in the interaction between sugars and their...
Article
We herein propose the use of the fluoroacetamide and difluoroacetamide moieties as sensitive tags for detecting sugar-protein interactions by simple 1H and/or 19F NMR methods. As selected process, we have chosen the binding of N,N'-diacetyl chitobiose, a ubiquitous disaccharide fragment in glycoproteins, by wheat germ agglutinin (WGA), a model lect...
Article
Full-text available
Ethylenediaminetetraacetic acid (EDTA) is a chelating agent commonly used in protein purification, both to eliminate contaminating divalent cations and to inhibit protease activity. For a number of subsequent applications EDTA needs to be exhaustively removed. Most purification methods rely in extensive dialysis and/or gel filtration in order to ex...
Chapter
This chapter is dedicated to the presentation of different examples of the application of solution NMR to the study of conformation, dynamics of sugar molecules (oligo and polysaccharides, glycopeptides and glycomimetics) and to the investigation of glycan-related molecular recognition events. Selected examples since 2012 are presented depending on...
Article
Full-text available
Background Glycosides are compounds displaying crucial biological roles and plenty of applications. Traditionally, these molecules have been chemically obtained, but its efficient production is limited by the lack of regio- and stereo-selectivity of the chemical synthesis. As an interesting alternative, glycosidases are able to catalyze the formati...
Article
Full-text available
The conformational analysis of the S and R diastereoisomers of benzyl 3-deoxy-4-S-(-D-galactopyranosyl)-4-thio-β-D-threo-pentopyranoside S-oxides (1S and 1R, respectively) has been performed by using NMR assisted by molecular modelling methods. The results point out that sulfoxide 1S and 1R display rather different conformational behavior, being 1S...
Article
Four natural analogues of podophyllotoxin obtained from the Mexican medicinal plant Bursera fagaroides, namely, acetyl podophyllotoxin (2), 5′-desmethoxy-β-peltatin A methyl ether (3), 7′,8′-dehydro acetyl podophyllotoxin (4), and burseranin (5), have been characterized, and their interactions with tubulin have been investigated. Cytotoxic activity...