A5063594309- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Immunotherapy and Immune Responses
- Neuropeptides and Animal Physiology
- Cholinesterase and Neurodegenerative Diseases
- Lysosomal Storage Disorders Research
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Catalytic Cross-Coupling Reactions
- Ubiquitin and proteasome pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Bacteriophages and microbial interactions
- Enzyme Production and Characterization
- Peptidase Inhibition and Analysis
- Algal biology and biofuel production
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Organoboron and organosilicon chemistry
- Biochemical and Molecular Research
Polytechnic Institute of Castelo Branco
2024
Universidade Nova de Lisboa
2014-2024
Unidade em Ciências Biomoleculares Aplicadas
2017-2024
Rede de Química e Tecnologia
2012-2022
Faculdade de Tecnologia e Ciências
2020
University of Florida
2016
Florida College
2016
Centro de Investigaciones Biológicas Margarita Salas
2009-2015
Consejo Superior de Investigaciones Científicas
2011-2015
Universidad de La Rioja
2014
Don't slam the door! Cyclodextrins capped with an N-heterocyclic carbene (ICyDs) entrapped metal ions within their cavity through a novel set of interactions, including X⋅⋅⋅π, which enabled to be closed by ligand exchange (see scheme; Bn=benzyl). Although insulated from electrode, deeply buried retained catalytic activity. The influenced regio- and stereochemical outcome catalyzed reactions. As service our authors readers, this journal provides supporting information supplied authors. Such...
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...
Amyloid peptides, Aβ1-40 and Aβ1-42, represent major molecular targets to develop potential drugs diagnostic tools for Alzheimer's Disease (AD). In fact, oligomeric fibrillar aggregates generated by these peptides are amongst the principal components of amyloid plaques found post mortem in patients suffering from AD. Rosmarinic acid has been demonstrated be effective preventing aggregation vitro delay progression disease animal models. Nevertheless, no information is available about its...
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
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...
Here we report the synthesis of a series polyhydroxylated 3- and 5-acetamido azepanes detail molecular basis their inhibition family 84 glycoside hydrolases. These enzymes include human O-GlcNAcase, an enzyme involved in post-translational processing intracellular proteins modified by O-linked beta-N-acetylglucosamine residues. Detailed structural analysis binding these to BtGH84, bacterial homologue highlights conformational flexibility. Molecular mechanics dynamics calculations reveal that...
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...
Geschlossene Gesellschaft: Mit einem N-heterocyclischen Carben überdeckte Cyclodextrine (ICyDs) binden in ihrem Hohlraum Metallionen unter Beteiligung von X⋅⋅⋅π-Wechselwirkungen, was ein Verschließen des Hohlraums durch Ligandenaustausch ermöglicht (siehe Schema; Bn=Benzyl). Obwohl kein elektrischer Kontakt mit einer Elektrode besteht, behalten die tief vergrabenen ihre katalytische Aktivität. Der beeinflusste den regio- und stereochemischen Verlauf der katalysierten Reaktionen.
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....
Abstract Two carbene‐based ligands have been attached to perbenzylated and permethylated cyclodextrins. Their palladium complexes were synthesized, characterized used as catalysts in Suzuki–Miyaura coupling reactions both ethanol water.
8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in treatment STZ-induced diabetic rats, producing normalization fasting hyperglycemia amelioration excessive postprandial glucose excursions increasing β-cell sensitivity, insulin secretion, circulating within 7 days at a dose 4 (mg/kg bw)/day. Suppression islet amyloid polypeptide (IAPP) fibril formation by compound 1 demonstrated thioflavin T fluorescence...
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...
Acetylcholinesterase (AChE) inhibition is one of the most currently available therapies for management Alzheimer's disease (AD) symptoms. In this context, NMR spectroscopy binding studies were accomplished to explain AChE activity by Salvia sclareoides extracts. HPLC-MS analyses acetone, butanol and water extracts eluted with methanol acidified showed that rosmarinic acid present in all studied samples a major constituent Moreover, luteolin 4'-O-glucoside, 3',7-di-O-glucoside...
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....