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

Autor: Michaela Hovorková, Pavla Bojarová, Jindřich Karban, Petra Cuřínová, Martin Dračínský, Vojtěch Hamala, Lucie Červenková Šťastná, Martin Kurfiřt
Rok vydání: 2021
Předmět:
Zdroj: Chemistry – A European Journal. 27:13040-13051
ISSN: 1521-3765
0947-6539
Popis: 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 19 F 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.
Databáze: OpenAIRE
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