A5067334070- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Microbial Metabolism and Applications
- Toxin Mechanisms and Immunotoxins
- Pharmacological Effects of Natural Compounds
- Bacterial Identification and Susceptibility Testing
Universidade Nova de Lisboa
2018-2025
Unidade em Ciências Biomoleculares Aplicadas
2021-2024
Rede de Química e Tecnologia
2018
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...
Glycopeptides derived from the mucin-1 (MUC1) glycoprotein hold significant promise as cancer vaccine candidates, but their clinical utility is limited by proteolytic degradation and poor bioavailability of L-α-amino acid-based peptides. In this study, we demonstrate that substitution multiple α-amino acids with homologous β-amino (same side chain, extended backbone) in O-glycosylated MUC1 derivatives significantly enhances stability. We further show α-to-β substitutions within most...
Abstract Overexpression of the Thomsen–Friedenreich (TF) antigen in cell membrane proteins occurs 90 % adenocarcinomas. Additionally, binding TF to human galectin‐3 (Gal‐3), also frequently overexpressed malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with specific interaction have potential prevent A multidisciplinary approach combining optimized synthesis a mimetic NMR, X‐ray crystallography methods, isothermal titration calorimetry assays...
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...
The mucin O-glycan sialyl Tn antigen (sTn, Neu5Acα2-6GalNAcα1-O-Ser/Thr) is an associated with different types of cancers, often linked a higher risk metastasis and poor prognosis. Despite efforts to develop anti-sTn antibodies high specificity for diagnostics immunotherapy, challenges in eliciting high-affinity glycan structures have limited their effectiveness, leading low titers short protection durations. Experimental structural insights into antibody are lacking, hindering optimization...