Selectively Deoxyfluorinated N-Acetyllactosamine Analogues as 19F NMR Probes to Study Carbohydrate-Galectin Interactions.

0544845 - ÚCHP 2022 RIV DE eng J - Journal Article
Kurfiřt, Martin - Dračínský, Martin - Červenková Šťastná, Lucie - Cuřínová, Petra - Hamala, Vojtěch - Hovorková, Michaela - Bojarová, Pavla - Karban, Jindřich
Selectively Deoxyfluorinated N-Acetyllactosamine Analogues as 19F NMR Probes to Study Carbohydrate-Galectin Interactions.
Chemistry - A European Journal. Roč. 27, č. 51 (2021), s. 13040-13051. ISSN 0947-6539. E-ISSN 1521-3765
R&D Projects: GA MŠMT(CZ) LTC20052; GA ČR(CZ) GA20-01472S; GA MŠMT(CZ) LTC19038
EU Projects: European Commission(XE) CA17140 - COST Action
Institutional support: RVO:67985858 ; RVO:61388963 ; RVO:61388971
Keywords : carbohydrates * ELISA * galectins * NMR spectroscopy * T2 filter
OECD category: Organic chemistry; Physical chemistry (UOCHB-X); Biochemistry and molecular biology (MBU-M)
Impact factor: 5.020, year: 2021
Method of publishing: Limited access

Galectins are widely expressed galactose-binding lectins implied, for example, in immune regulation, metastatic spreading, and pathogen recognition. N-Acetyllactosamine (Galβ1-4GlcNAc, LacNAc) and its oligomeric or glycosylated forms are natural ligands of galectins. To probe substrate specificity and binding mode of galectins, we synthesized a complete series of six mono-deoxyfluorinated analogues of LacNAc, in which each hydroxyl has been selectively replaced by fluorine while the anomeric position has been protected as methyl β-glycoside. Initial evaluation of their binding to human galectin-1 and -3 by ELISA and 19F NMR T2-filter revealed that deoxyfluorination at C3, C4′ and C6′ completely abolished binding to galectin-1 but very weak binding to galectin-3 was still detectable. Moreover, deoxyfluorination of C2′ caused an approximately 8-fold increase in the binding affinity towards galectin-1, whereas binding to galectin-3 was essentially not affected. Lipophilicity measurement revealed that deoxyfluorination at the Gal moiety affects log P very differently compared to deoxyfluorination at the GlcNAc moiety.
Permanent Link: http://hdl.handle.net/11104/0321651