Synthesis and unexpected binding of monofluorinated N,N'-diacetylchitobiose and LacdiNAc to wheat germ agglutinin
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
38705105
DOI
10.1016/j.bioorg.2024.107395
PII: S0045-2068(24)00300-6
Knihovny.cz E-zdroje
- Klíčová slova
- Alchemical free energy calculation, Chemical synthesis, Conformational analysis, ELLA, Fluorinated carbohydrates, Nuclear magnetic resonance, Wheat germ agglutinin,
- MeSH
- acetylglukosamin chemie metabolismus MeSH
- aglutininy z pšeničných klíčků * chemie metabolismus MeSH
- disacharidy * chemie chemická syntéza MeSH
- halogenace MeSH
- laktosa analogy a deriváty MeSH
- molekulární struktura MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- N-acetylgalactosaminyl-1-4-N-acetylglucosamine MeSH Prohlížeč
- N,N-diacetylchitobiose MeSH Prohlížeč
Fluorination of carbohydrate ligands of lectins is a useful approach to examine their binding profile, improve their metabolic stability and lipophilicity, and convert them into 19F NMR-active probes. However, monofluorination of monovalent carbohydrate ligands often leads to a decreased or completely lost affinity. By chemical glycosylation, we synthesized the full series of methyl β-glycosides of N,N'-diacetylchitobiose (GlcNAcβ(1-4)GlcNAcβ1-OMe) and LacdiNAc (GalNAcβ(1-4)GlcNAcβ1-OMe) systematically monofluorinated at all hydroxyl positions. A competitive enzyme-linked lectin assay revealed that the fluorination at the 6'-position of chitobioside resulted in an unprecedented increase in affinity to wheat germ agglutinin (WGA) by one order of magnitude. For the first time, we have characterized the binding profile of a previously underexplored WGA ligand LacdiNAc. Surprisingly, 4'-fluoro-LacdiNAc bound WGA even stronger than unmodified LacdiNAc. These observations were interpreted using molecular dynamic calculations along with STD and transferred NOESY NMR techniques, which gave evidence for the strengthening of CH/π interactions after deoxyfluorination of the side chain of the non-reducing GlcNAc. These results highlight the potential of fluorinated glycomimetics as high-affinity ligands of lectins and 19F NMR-active probes.
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