A5046162926- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Mass Spectrometry Techniques and Applications
- Plant tissue culture and regeneration
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Infant Nutrition and Health
- Traditional and Medicinal Uses of Annonaceae
- Plant Reproductive Biology
- Plant Molecular Biology Research
- Phytochemical compounds biological activities
- Fluorine in Organic Chemistry
- Escherichia coli research studies
- Plant biochemistry and biosynthesis
- Lung Cancer Treatments and Mutations
- Cancer therapeutics and mechanisms
- Biochemical effects in animals
- Peptidase Inhibition and Analysis
- Food Quality and Safety Studies
- Phytoestrogen effects and research
- Phytase and its Applications
- Proteoglycans and glycosaminoglycans research
- Lanthanide and Transition Metal Complexes
Universidad de La Rioja
2012-2023
CIC biomaGUNE
2021-2023
Utrecht University
2017-2020
University of Cambridge
2015-2017
Chemical modification of proteins is essential for a variety important diagnostic and therapeutic applications. Many strategies developed to date lack chemo- regioselectivity as well result in non-native linkages that may suffer from instability vivo adversely affect the protein's structure function. We describe here reaction N-nucleophiles with amino acid dehydroalanine (Dha) protein context. When Dha chemically installed proteins, addition wide-range enables rapid formation amine...
Abstract The structural features of MUC1‐like glycopeptides bearing the Tn antigen (α‐ O ‐GalNAc‐Ser/Thr) in complex with an anti MUC‐1 antibody are reported at atomic resolution. For α‐ ‐GalNAc‐Ser derivative, glycosidic linkage adopts a high‐energy conformation, barely populated free state. This unusual structure (also observed S ‐GalNAc‐Cys mimic) is stabilized by hydrogen bonds between peptidic fragment and sugar. selection particular peptide thus propagated to carbohydrate through...
A structure-based design of a new generation tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature fluorinated proline residue, such as (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic domain. Binding assays using biolayer interferometry reveal 3-fold to 10-fold improvement respect natural (glyco)peptides. According X-ray crystallography and MD simulations, residues stabilize...
Abstract The voltage‐dependent L‐type Ca 2+ channel was identified as a macromolecular target for (−)‐englerin A. This finding reached by using an unprecedented ligand‐based prediction platform and the natural product piperlongumine pharmacophore probe. (−)‐Englerin A features high substructure dissimilarity to known ligands channels, selective binding affinity dihydropyridine site, potent modulation of calcium signaling in muscle cells vascular tissue. observed activity rationalized at...
Tn antigen (α-O-GalNAc-Ser/Thr) is a convenient cancer biomarker that recognized by antibodies and lectins. This work yields remarkable results for two plant lectins in terms of epitope recognition reveals these receptors show higher affinity when it incorporated the Pro-Asp-Thr-Arg (PDTR) peptide region mucin MUC1. In contrast, significant loss observed located Ala-His-Gly-Val-Thr-Ser-Ala (AHGVTSA) or Ala-Pro-Gly-Ser-Thr-Ala-Pro (APGSTAP) fragments. Our data indicate charged residues, Arg...
Abstract The molecular recognition of several glycopeptides bearing Tn antigen (α‐ O ‐GalNAc‐Ser or α‐ ‐GalNAc‐Thr) in their structure by three lectins with affinity for this determinant has been analysed. work yields remarkable results terms epitope recognition, showing that the underlying amino acid (serine threonine) plays a key role recognition. In fact, while Soybean agglutinin and Vicia villosa prefer Tn‐threonine, Helix pomatia shows higher carrying Tn‐serine. different conformational...
The first examples of amino acid (Ser/Thr)–sp2-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. key synthetic step involves the completely diastereoselective α-glycosylation Ser/Thr due to strong stereoelectronic and conformational bias imposed by bicyclic sp2-iminosugar scaffold. Mucin-related glycopeptides incorporating these motifs were recognized monoclonal antibody (mAb) scFv-SM3, with activities depending on both hydroxylation pattern...
Multivalent carbohydrate-based ligands were synthesized and evaluated as inhibitors of the adhesion protein HA influenza A virus (IAV). relies on multivalency for strong viral adhesion. While inhibition by large polymeric molecules has proven viable, limited success was reached smaller multivalent compounds. By linking sialylated LAcNAc units to di- trivalent scaffolds, obtained with an up 428-fold enhanced in various assays.
Abstract The fucosylation of glycans leads to diverse structures and is associated with many biological disease processes. exact determination fucoside positions by tandem mass spectrometry (MS/MS) complicated because rearrangements in the gas phase lead erroneous structural assignments. Here, we demonstrate that combined use ion‐mobility MS well‐defined synthetic glycan standards can prevent misinterpretation MS/MS spectra incorrect assignments fucosylated glycans. We show fucosyl residues...
Glycans possess unparalleled structural complexity arising from chemically similar monosaccharide building blocks, configurations of anomeric linkages and different branching patterns, potentially giving rise to many isomers. This level is one the main reasons that identification exact glycan structures in biological samples still lags behind other biomolecules. Here, we introduce a methodology identify isomeric N-glycans by determining gas phase conformer distributions (CDs) measuring...
2,4-dichlorophenoxyacetic acid (2,4-D) is a synthetic analogue of the plant hormone auxin that commonly used in many vitro regeneration systems, such as somatic embryogenesis (SE). Its effectiveness inducing SE, compared to natural indole-3-acetic (IAA), has been attributed stress triggered by this compound rather than its auxinic activity. However, hypothesis never thoroughly tested. Here we library forty 2,4-D analogues test structure-activity relationship with respect capacity induce SE...
Pathological glycation of extracellular matrix modelled with<sup>13</sup>C-labelled sugars yields unique novel atomic level NMR structural and chemical insights non-destructively.
Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. be effective and stimulate an anti-MUC1 response, artificial must mimic the conformational dynamics of natural solution have equivalent or higher binding affinity to antibodies than counterparts. As proof concept, developed...
Abstract The voltage‐dependent L‐type Ca 2+ channel was identified as a macromolecular target for (−)‐englerin A. This finding reached by using an unprecedented ligand‐based prediction platform and the natural product piperlongumine pharmacophore probe. (−)‐Englerin A features high substructure dissimilarity to known ligands channels, selective binding affinity dihydropyridine site, potent modulation of calcium signaling in muscle cells vascular tissue. observed activity rationalized at...
Abstract The structural features of MUC1‐like glycopeptides bearing the Tn antigen (α‐ O ‐GalNAc‐Ser/Thr) in complex with an anti MUC‐1 antibody are reported at atomic resolution. For α‐ ‐GalNAc‐Ser derivative, glycosidic linkage adopts a high‐energy conformation, barely populated free state. This unusual structure (also observed S ‐GalNAc‐Cys mimic) is stabilized by hydrogen bonds between peptidic fragment and sugar. selection particular peptide thus propagated to carbohydrate through...
Erlotinib is a first-generation epithelial growth factor receptor inhibitor used in the treatment of non-small cellular lung cancers. Our previously published method on Thermo TSQ Quantum Ultra triple quadrupole mass spectrometer for quantitation erlotinib, OSI-420, and OSI-413 some other kinase inhibitors was transferred to more sensitive Sciex QTRAP5500 system. Both methods showed comparable performance previous range (5–5000 1–1000 ng/mL erlotinib OSI-420) with accuracies precisions...
Abstract The fucosylation of glycans leads to diverse structures and is associated with many biological disease processes. exact determination fucoside positions by tandem mass spectrometry (MS/MS) complicated because rearrangements in the gas phase lead erroneous structural assignments. Here, we demonstrate that combined use ion‐mobility MS well‐defined synthetic glycan standards can prevent misinterpretation MS/MS spectra incorrect assignments fucosylated glycans. We show fucosyl residues...
Human milk oligosaccharides (HMOs) and their most abundant component, 2'-Fucosyllactose (2'-FL), are known to be immunomodulatory. Previously, it was shown that HMOs 2'-FL bind the C-type lectin receptor DC-SIGN. Here we show, using a ligand-receptor competition assay, whole mixture of from pooled human (HMOS) inhibit binding carbohydrate-binding DC-SIGN its prototypical ligands, fucose oligosaccharide Lewis-B, (Leb) in dose-dependent way. Interestingly, such inhibition by HMOS not detected...
Cys-Xxx-Ser-Xxx-Pro-Cys (Xxx= any amino acid but Pro) is the most common sequence present in naturally occurring peptides and proteins glycosylated with β-O-glucose (β-O-Glc). Taking into account lack of studies concerning spatial disposition this sequence, we have synthesized analyzed, aqueous solution, conformational behavior a glycopeptide derived from particular fragment Cys-Ala-Ser-Ser-Pro-Cys. This found crystal structure complex blood coagulation factor VIIa soluble tissue factor. Our...
Abstract The design of mimic molecules that resemble natural products can be a useful tool to help understand the key aspects in molecular recognition processes are difficult access by using derivatives. We present synthesis and conformational analysis different glucosylated diamide amino acids simulate glycopeptides with β‐O‐linked glucose contain nonnatural β‐hydroxycyclohexane‐α‐amino acid. study, NMR experiments, X‐ray spectroscopy, dynamics simulations, reveals cyclohexane ring allows...
Abstract Human milk oligosaccharides (HMOs) and its most abundant component, 2’-Fucosyllactose (2’-FL), are known to be immunomodulatory. Previously, it was shown that HMOs 2’-FL bind the C-type lectin receptor DC-SIGN. Here we show, using a ligand-receptor competition assay, whole mixture of from pooled human (HMOS) inhibit binding carbohydrate-binding DC-SIGN prototypical ligands, fucose oligosaccharide Lewis-B, (Le b ) in dose-dependent way. Interestingly, such inhibition by HMOS not...