A5077818736- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Escherichia coli research studies
- Immune Response and Inflammation
- Alzheimer's disease research and treatments
- Antimicrobial Peptides and Activities
- Food Quality and Safety Studies
- Lipid Membrane Structure and Behavior
- Immunodeficiency and Autoimmune Disorders
- Fibroblast Growth Factor Research
- Cholinesterase and Neurodegenerative Diseases
- Medicinal plant effects and applications
- Lanthanide and Transition Metal Complexes
- Parathyroid Disorders and Treatments
- Erythrocyte Function and Pathophysiology
- Pediatric health and respiratory diseases
- Phytoestrogen effects and research
- Mast cells and histamine
- Bacteriophages and microbial interactions
- Lysosomal Storage Disorders Research
Universidade Nova de Lisboa
2015-2024
Unidade em Ciências Biomoleculares Aplicadas
2021-2024
CIC bioGUNE
2017-2022
University of the Basque Country
2017-2022
Rede de Química e Tecnologia
2014-2022
Zero to Three
2021
Faculdade de Tecnologia e Ciências
2020
Instituto de Biologia Experimental e Tecnológica
2015
Universidad de La Rioja
2014
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
Abstract Sialic acid-binding Ig-like lectin 15 (Siglec-15) is an immune modulator and emerging cancer immunotherapy target. However, limited understanding of its structure mechanism action restrains the development drug candidates that unleash full therapeutic potential. In this study, we elucidate crystal Siglec-15 binding epitope via co-crystallization with anti-Siglec-15 blocking antibody. Using saturation transfer-difference nuclear magnetic resonance (STD-NMR) spectroscopy molecular...
The human macrophage galactose lectin (MGL) is an endocytic type II transmembrane receptor expressed on immature monocyte-derived dendritic cells and activated macrophages plays a role in modulating the immune system response to infections cancer. MGL contains extracellular calcium-dependent (C-type) carbohydrate recognition domain (CRD) that specifically binds terminal N-acetylgalactosamine glycan residues such as Tn sialyl-Tn antigens found tumor cells, well other N- O-glycans displayed...
Abstract The human macrophage galactose‐type lectin (MGL) is a key physiological receptor for the carcinoma‐associated Tn antigen (GalNAc‐α‐1‐ O ‐Ser/Thr) in mucins. NMR and modeling‐based data on molecular recognition features of synthetic Tn‐bearing glycopeptides by MGL are presented. Cognate epitopes sugar matching amino acids involved interaction were identified saturation transfer difference (STD) spectroscopy. Only close to glycosylation site peptides contact. Moreover, control...
The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and lectin domain connected by flexible linker. In addition to recognizing sequence, the GalNAc-Ts exhibit unique long-range N- and/or C-terminal prior glycosylation (GalNAc-O-Ser/Thr) preferences modulated domain. Here we report studies on GalNAc-T4 reveal origins its N-terminal glycopeptide specificity, which is opposite GalNAc-T2. structure bound monoglycopeptide shows...
Mucin-type O-glycosylation is initiated by a family of polypeptide GalNAc-transferases (GalNAc-Ts) which are type-II transmembrane proteins that contain Golgi luminal catalytic and lectin domains connected flexible linker. Several GalNAc-Ts, including GalNAc-T4, show both long-range short-range prior glycosylation specificity, governed their domains, respectively. While the mechanism lectin-domain-dependent well-known, molecular basis for catalytic-domain-dependent glycopeptides unclear....
Human sialic-acid-binding immunoglobulin-like lectin-9 (Siglec-9) is a glycoimmune checkpoint receptor expressed on several immune cells. Binding of Siglec-9 to sialic acid containing glycans (sialoglycans) well documented modulate its functions as an inhibitory receptor. Here, we first assigned the amino backbone V-set domain (Siglec-9
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...
The identification of MUC1 tumor-associated Tn antigen (αGalpNAc1-O-Ser/Thr) has boosted the development anticancer vaccines. Combining microarrays and saturation transfer difference NMR, we have characterized fine-epitope mapping a chemical library (naked Tn-glycosylated) toward two families cancer-related monoclonal antibodies (anti-MUC1 anti-Tn mAbs). Anti-MUC1 mAbs clone VU-3C6 VU-11E2 recognize naked MUC1-derived peptides bind GalNAc in peptide-sequence-dependent manner. In contrast,...
The large family of polypeptide GalNAc-transferases (GalNAc-Ts) controls with precision how GalNAc O-glycans are added in the tandem repeat regions mucins (e.g., MUC1). However, structural features behind creation well-defined and clustered patterns poorly understood. In this context, herein, we disclose full process MUC1 O-glycosylation by GalNAc-T2/T3/T4 isoforms NMR spectroscopy assisted molecular modeling protocols. By using MUC1, four domains as a substrate, confirmed glycosylation...
Abstract C1GalT1 is an essential inverting glycosyltransferase responsible for synthesizing the core 1 structure, a common precursor mucin-type O -glycans found in many glycoproteins. To date, structure of and details substrate recognition catalysis remain unknown. Through biophysical cellular studies, including X-ray crystallography complexed to glycopeptide, we report that obligate GT-A fold dimer follows S N 2 mechanism. The binding glycopeptides enzyme mainly driven by GalNAc moiety...
Abstract The human macrophage galactose‐type lectin (MGL), expressed on macrophages and dendritic cells (DCs), modulates distinct immune cell responses by recognizing N ‐acetylgalactosamine (GalNAc) containing structures present pathogens, self‐glycoproteins, tumor cells. Herein, NMR spectroscopy molecular dynamics (MD) simulations were used to investigate the structural preferences of MGL against different GalNAc‐containing derived from blood group A antigen, Forssman GM2 glycolipid....
Abstract New monosaccharide-based lipid A analogues were rationally designed through MD-2 docking studies. panel of compounds with two carboxylate groups as phosphates bioisosteres, was synthesized the same glucosamine-bis-succinyl core linked to different unsaturated and saturated fatty acid chains. The binding synthetic purified, functional recombinant human studied by four independent methods. All bound similar affinities inhibited in a concentration-dependent manner LPS-stimulated TLR4...
Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such allergic airway inflammation. Herein, we have deciphered the molecular recognition features interaction with mAb lirentelimab (2C4, under...
Glycosylation is a critical post-translational modification that plays pivotal role in several biological processes, such as the immune response. Alterations glycosylation can modulate course of various pathologies, case congenital disorders (CDG), group more than 160 rare and complex genetic diseases. Although link between dysfunction has already been recognized, involvement most CDG remains largely unexplored poorly understood. In this study, we provide an update on clinical manifestations...
The molecular basis of an anti-MUC1 antibody that recognizes the entire GalNAc unit as a primary epitope is disclosed.
Abstract The family of polypeptide N ‐acetylgalactosamine (GalNAc) transferases (GalNAc‐Ts) orchestrates the initiating step mucin‐type protein O‐glycosylation by transfer GalNAc moieties to serine and threonine residues in proteins. Deficiencies dysregulation GalNAc‐T isoenzymes are related different diseases. Recently, it has been demonstrated that an inactive GalNAc‐T2 mutant (F104S), which is not located at active site, induces low levels high‐density lipoprotein cholesterol (HDL‐C)...
Abstract 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 13 C‐labelled glycans with lectins, which are organs tissues that may be affected during infection process, has also evaluated In particular, 15 N‐labelled galectins (galectins‐3, ‐7...
Abstract Interactions of glycan‐specific epitopes to human lectin receptors represent novel immune checkpoints for investigating cancer and infection diseases. By employing a multidisciplinary approach that combines isothermal titration calorimetry, NMR spectroscopy, molecular dynamics simulations, X‐ray crystallography, we investigated the determinants govern recognition tumour pathogenic glycobiomarker LacdiNAc (GalNAcβ1‐4GlcNAc, LDN), including their comparison with ubiquitous LacNAc...
Alzheimer's disease is a grave social problem in an aging population. A major the passage of drugs through blood–brain barrier. This work tests hypothesis that conjugation peptidomimetic β-secretase inhibitors with fragment amyloid-β peptide facilitates entrance into central nervous system. HVR-3 (compound 4), one products, was found to be as potent OM00-3, known inhibitor, 4-fold more selective toward 1 relation 2 and 3-fold resistant vitro metabolization human serum. Its intravenous...
This study examines the effect of co-administration antimicrobial peptides and synthetic glycolipid FP7, which is active in inhibiting inflammatory cytokine production caused by TLR4 activation signaling. The two lipopolysaccharide (LPS)-neutralizing (a cecropin A-melittin hybrid peptide a human cathelicidin) enhances an order magnitude potency FP7 blocking signal. Interestingly, this not additional LPS neutralization peptides, because it also occurs if cells are stimulated plant lectin...