Synthesis and unexpected binding of monofluorinated N,Nʹ-diacetylchitobiose and LacdiNAc to wheat germ agglutinin.

0585671 - ÚCHP 2025 RIV NL eng J - Journal Article
Kurfiřt, Martin - Hamala, Vojtěch - Beránek, J. - Červenková Šťastná, Lucie - Červený, Jakub - Dračínský, Martin - Bernášková, Jana - Spiwok, V. - Bosáková, Z. - Bojarová, Pavla - Karban, Jindřich
Synthesis and unexpected binding of monofluorinated N,Nʹ-diacetylchitobiose and LacdiNAc to wheat germ agglutinin.
Bioorganic Chemistry. Roč. 147, June 2024 (2024), č. článku 107395. ISSN 0045-2068. E-ISSN 1090-2120
R&D Projects: GA ČR(CZ) GA23-05146S; GA MŠMT(CZ) LTC20052; GA MŠMT(CZ) LM2023055
Grant - others:MEYS(XE) CA18103
Research Infrastructure: e-INFRA CZ II - 90254
Institutional support: RVO:67985858 ; RVO:61388971 ; RVO:61388963
Keywords : fluorinated carbohydrates * chemical synthesis * wheat germ agglutinin * ELLA
OECD category: Organic chemistry; Organic chemistry (UOCHB-X); Organic chemistry (MBU-M)
Impact factor: 5.1, year: 2022
Method of publishing: Open access with time embargo

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 highaffinity ligands of lectins and 19F NMR-active probe.
Permanent Link: https://hdl.handle.net/11104/0353359