A5025486809- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Catalytic Alkyne Reactions
- Catalytic C–H Functionalization Methods
- Peptidase Inhibition and Analysis
- Protein Structure and Dynamics
- Crystallography and molecular interactions
- Toxin Mechanisms and Immunotoxins
- Monoclonal and Polyclonal Antibodies Research
- Proteoglycans and glycosaminoglycans research
- Immunotherapy and Immune Responses
- Chemical Synthesis and Analysis
- Alzheimer's disease research and treatments
- Asymmetric Hydrogenation and Catalysis
- Computational Drug Discovery Methods
- Catalytic Cross-Coupling Reactions
- Catalysis and Oxidation Reactions
- Pneumonia and Respiratory Infections
- Catalysis and Hydrodesulfurization Studies
- Protein Kinase Regulation and GTPase Signaling
- Amphibian and Reptile Biology
- Education in Diverse Contexts
Digital Research Alliance of Canada
2021-2024
CIC bioGUNE
2017-2024
Utrecht University
2024
Ikerbasque
2024
Euskadiko Parke Teknologikoa
2017-2021
Boeing (Spain)
2021
University of Salzburg
2010-2021
Instituto de Salud Carlos III
2021
University of the Basque Country
2020
Instituto Geológico y Minero de España
2020
Very often ligands are anionic or neutral species. Cationic ones rare, and, when used, the positively charged groups normally appended to periphery of ligand. Here, we describe a dicationic phosphine with no spacer between phosphorus atom and two groups. This structural feature makes its donor ability poorer than that phosphites only comparable extremely toxic pyrophoric compounds such as PF3 P(CF3)3. By exploiting these properties, new Au catalyst has been developed displaying dramatically...
The glycan structures of the receptor binding domain SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR. different possible interacting epitopes deeply analysed and characterized, providing evidence presence not found previous MS-based analyses. interaction RBD
Human dynamin-1-like protein (DNM1L) is a GTP-driven molecular machine that segregates mitochondria and peroxisomes. To obtain insights into its catalytic mechanism, we determined crystal structures of construct comprising the GTPase domain bundle signaling element (BSE) in nucleotide-free GTP-analogue-bound states. The DNM1L structurally related to dynamin binds nucleotide 5′-Guanylyl-imidodiphosphate (GMP-PNP) via five highly conserved motifs, whereas BSE folds pocket at opposite side....
Ligand conformational entropy plays an important role in carbohydrate recognition events. Glycans are characterized by intrinsic flexibility around the glycosidic linkages, thus most cases, loss of sugar upon complex formation strongly affects binding process. By employing a multidisciplinary approach combining structural, conformational, energy, and kinetic information, we investigated histo blood-group antigens A B human galectin-3, lectin biomedical interest. We show that these rigid...
The zwitterionic Streptococcus pneumoniae serotype 1 polysaccharide (Sp1) is an important anchor point for our immune system to act against streptococcal infections. Antibodies can recognize Sp1 saccharides, and it has been postulated that elicit a T-cell-dependent reaction as be presented by MHC-II molecules. To unravel the molecular mode of action this unique we here describe chemical synthesis set fragments, ranging from 3 12 monosaccharides in length. We outline synthetic approach...
The competition between π- and dual σ,π-gold-activation modes is revealed in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable effect various ligands gold complexes on choice these activation described. cationic [Au(IPr)](+) (IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes π terminal alkynes, whereas [Au(PtBu3 )](+) favors intermediate σ,π species. In this experimental mechanistic study, which includes kinetic cross-over experiments,...
α,β-Unsaturated N,N-dialkyl hydrazones undergo a mild [2 + 2] cycloaddition to allenamides when treated with suitable gold catalyst. The method, which represents the first application of in catalysis, is compatible wide variety substituents at alkenyl moiety hydrazone component, proceeds excellent levels regio- and diastereoselectivity, provides densely substituted cyclobutanes good yields.
The dynamic adaptability of tetragonal prismatic nanocapsule 18+ in the selective separation fullerenes and endohedral metallofullerenes (EMFs) remains unexplored. Therefore, essential molecular details fullerene recognition binding process into coordination capsule origins selectivity remain elusive. In this work, key steps processes have been deciphered by designing a protocol which combines 1H–1H exchange spectroscopy (2D-EXSY) NMR experiments, long time-scale Molecular Dynamics (MD)...
3-Substituted 1-(o-ethynylaryl)ureas 1 selectively undergo either 6-exo-dig or 5-endo-dig cyclization (to give 4-methylene-3,4-quinazolin-2-ones 2 indoles 3, respectively) depending on the choice of metal, ligand, and reaction conditions. The best results (up to 96% yield) in preparation hydroamination products are achieved with highly bulky NHC-stabilized cationic gold(I) complex [Au(IPr)](+). Conversely, ureas bearing an internal alkyne lead mode regardless employed. Whereas nature...
Glycans play a key role as recognition elements in the communication of cells and other organisms. Thus, analysis carbohydrate-protein interactions has gained significant importance. In particular, nuclear magnetic resonance (NMR) techniques are considered powerful tools to detect relevant features interaction between sugars their natural receptors. Here, we present results obtained study on molecular different mannose-containing glycans by Pisum sativum agglutinin. NMR experiments supported...
Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable effects towards jack bean α-mannosidase and Golgi from Drosophila melanogaster, as well good selectivity with respect to lysosomal α-mannosidase, which is important for anticancer applications. STD NMR molecular modeling studies supported mechanism specific interactions of the bioactive iminosugars Jack α-mannosidase. TEM suggested binding mode that involves formation aggregates, result...
The interaction of human galectin-1 with a variety oligosaccharides, from di-(N-acetyllactosamine) to tetra-saccharides (blood B type-II antigen) has been scrutinized by using combined approach different NMR experiments, molecular dynamics (MD) simulations, and isothermal titration calorimetry. Ligand- receptor-based experiments assisted computational methods allowed proposing three-dimensional structures for the complexes, which explained lack enthalpy gain when increasing chemical...
Transthyretin (TTR) modulates the deposition, processing, and toxicity of Abeta (Aβ) peptides. We have shown that this effect is enhanced in mice by treatment with small molecules such as iododiflunisal (IDIF, 4), a good TTR stabilizer. Here, we describe thermodynamics formation binary ternary complexes among TTR, Aβ(1–42) peptide, stabilizers using isothermal titration calorimetry (ITC). A TTR/Aβ(1–42) (1:1) complex dissociation constant Kd = 0.94 μM formed; IDIF (4), improves up to 0.32...
A combined chemo-enzymatic synthesis/NMR-based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when protein receptors. The concept based on incorporation of 13 C-labels at specific monosaccharide units, selected a glycan oligomeric structure. No new chemical tags are added, and thus entity remains same, while presence C-labeled breaks NMR shift degeneracy that occurs non-labeled compound allows unique...
Transthyretin (TTR) has a well-established role in neuroprotection Alzheimer's Disease (AD). We have setup drug discovery program of small-molecule compounds that act as chaperones enhancing TTR/Amyloid-beta peptide (Aβ) interactions. A combination computational repurposing approaches and vitro biological assays resulted set molecules which were then screened with our in-house validated high-throughput screening ternary test. prioritized list was obtained corroborated ITC studies....
Several strategies against Alzheimer disease (AD) are directed to target Aβ-peptides. The ability of transthyretin (TTR) bind Aβ-peptides and the positive effect exerted by some TTR stabilizers for modulating TTR-Aβ interaction have been previously studied. Herein, key structural features between Aβ(12-28) peptide (3), essential recognition element Aβ, unravelled STD-NMR spectroscopy methods in solution. Molecular aspects related role stabilizer iododiflunisal (IDIF, 5) on complex also...
Unactivated alkenes and 1,3-unsubstituted indoles in gold(<sc>i</sc>)-catalysed hydroaminative/arylative cascade cyclizations.
Significance The elucidation of structural epitopes is key to understanding the mechanisms action vaccines. Here a multidisciplinary approach was used map glycan epitope Neisseria meningitidis serogroup A capsular polysaccharide, component marketed vaccines, with monoclonal antibody capable triggering human complement-mediated bactericidal killing. found be composed trisaccharide motif, in which acetylation moieties play pivotal role binding. This study will guide design improved vaccines...
Abstract Readily available 1‐( ortho ‐ethynylaryl)urea derivatives undergo a selective gold/silver {[AuCl(IPr)]/AgSbF 6 } catalyzed N ‐6‐ exo ‐dig or ‐5‐ endo heterocyclization process in dimethylformamide (DMF) at 60 °C. Benzoxazine derivatives, i.e., the products of O ring closure through urea oxygen, could be observed under catalytic conditions only when ‐3 basicity was substantially diminished, but were readily isolable stoichiometric processes carried out low temperature. The open chain...