Molecules, Journal Year: 2024, Volume and Issue: 29(16), P. 3980 - 3980
Published: Aug. 22, 2024
The presence and the level of antibodies in human sera against bacterial glycans are indications prior encounters with similar antigens and/or bacteria that express them by immune system. An increasing number pathogenic cause diseases have been shown to polysaccharides containing a nonulosonic acid called 5,7-di-
Language: Английский
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Nov. 8, 2024
Access to defined glycans and glycoconjugates is pivotal for discovery, dissection, harnessing of a range biological functions orchestrated by cellular glycosylation processes the glycome. We previously employed genetic glycoengineering nuclease-based gene editing develop sustainable production designer glycoprotein therapeutics cell-based glycan arrays that display in their natural context at cell surface. However, access human formats quantities allow structural studies molecular interactions use biomedical applications currently rely on chemical chemoenzymatic syntheses associated with considerable labor, waste, costs. Here, we scalable method glycoengineered mammalian cells employing secreted Glycocarriers repeat acceptor sequence motifs different glycans. The Glycocarrier technology provides flexible platform formats, including oligosaccharides, glycopeptides, multimeric glycomodules, offers wide opportunities bioassays applications.
Language: Английский
Citations
4
Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Most cells are decorated with distinct sugar sequences that can be recognized by carbohydrate-binding proteins (CBPs), such as antibodies and lectins. While humans utilize ten monosaccharide building blocks, bacteria biosynthesize hundreds of activated sugars to assemble diverse glycans. Monosaccharides absent in mammals termed "rare" enriched deoxy l-sugars beyond the "common" l-fucose (l-Fuc) found across species. immune recognize microbial surfaces, there limited probes identify CBPs for many rare may mediate these interactions. Here, we devise chemoenzymatic strategies defined glycoconjugates containing l-Fuc its structural analog l-colitose (l-Col), a bacterial dideoxysugar believed bind proteins. We report concise synthesis l-Col semisynthetic routes several l-sugars. Incorporation into glycans is evaluated using mammalian glycosyltransferases (GTs) annotated transfer or l-Fuc, respectively. find each GT both l-sugars, along hexose l-galactose (l-Gal), onto various glycan acceptors. resulting confirmed known CBPs. Finally, ligands employed detect sugar-binding human serum. Overall, this work reveals similarities between GTs exploited vitro glycoconjugate construction unveil novel mediators host-pathogen
Language: Английский
Citations
0
Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14
Published: Jan. 1, 2025
Language: Английский
Citations
0
ACS Central Science, Journal Year: 2025, Volume and Issue: unknown
Published: April 23, 2025
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1535 - 1535
Published: Feb. 12, 2025
Fluorination of carbohydrates is a promising strategy to produce glycomimetics with improved pharmacological properties, such as increased metabolic stability, bioavailability and protein-binding affinity. Fluoroglycans are not only interest inhibitors chemical probes but increasingly being used develop potential synthetic vaccine candidates for cancer, HIV bacterial infections. Despite their attractiveness, the synthesis fluorinated oligosaccharides still challenging, emphasizing need efficient protocols that allow site-specific incorporation fluorine atoms (especially at late stages synthesis). This particularly true development fully candidates, whose (modified) carbohydrate antigen structures (glycotopes) per se comprise multistep routes. Based on known minimal protective epitope from capsular polysaccharide S. pneumoniae serotype 8, panel six novel F-glycotope mimetics was synthesized, equipped amine linkers subsequent conjugation immunogens. Next stepwise assembly via building blocks, corresponding 6F-substituted derivatives could be obtained by microwave-assisted, nucleophilic late-stage fluorination tri- tetrasaccharidic precursors in high yields. The described allowed preparation targeted sufficient quantities future immunological studies.
Language: Английский
Citations
0
Molecular & Cellular Proteomics, Journal Year: 2024, Volume and Issue: unknown, P. 100844 - 100844
Published: Sept. 1, 2024
Language: Английский
Citations
2
Glycobiology, Journal Year: 2024, Volume and Issue: 34(11)
Published: Aug. 2, 2024
Abstract IgA nephropathy is a kidney disease characterized by deposition of immune complexes containing abnormally O-glycosylated IgA1 in the glomeruli. Specifically, some O-glycans are missing galactose that normally β1,3-linked to N-acetylgalactosamine core 1 glycans. These galactose-deficient glycoforms produced IgA1-secreting cells due dysregulated expression and activity several glycosyltransferases. Galactose-deficient circulation patients with bound IgG autoantibodies resultant can contain additional proteins, such as complement C3. complexes, if not removed from circulation, enter glomerular mesangium, activate resident mesangial cells, induce injury. In this review, we briefly summarize clinical pathological features nephropathy, review normal aberrant O-glycosylation pathways, discuss origins potential significance natural anti-glycan antibodies, namely those recognizing N-acetylgalactosamine. We also specific for characteristics pathogenic IgG. kidneys injured IgA1-containing innocent bystanders. Most progress failure require dialysis or transplantation. Moreover, most after transplantation experience recurrent disease. Thus, better understanding pathogenetic mechanisms needed develop new disease-specific treatments.
Language: Английский
Citations
1
Talanta, Journal Year: 2024, Volume and Issue: 283, P. 127120 - 127120
Published: Oct. 30, 2024
Language: Английский
Citations
1
Molecules, Journal Year: 2024, Volume and Issue: 29(16), P. 3980 - 3980
Published: Aug. 22, 2024
The presence and the level of antibodies in human sera against bacterial glycans are indications prior encounters with similar antigens and/or bacteria that express them by immune system. An increasing number pathogenic cause diseases have been shown to polysaccharides containing a nonulosonic acid called 5,7-di-
Language: Английский
Citations
1