Abstract
A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9C, and 9N revealed that the galactosides selectively bound galectin-9C, whereas the gulosides selectively bound galectin-9N. Hence, the N-aryl group induces galectin-9 selectivity and the ligand 3C-configuration acts as an epimeric selectivity switch between the two domains of galectin-9. Furthermore, MD simulations revealed that galacto derivatives in galectin-9C and gulo derivatives in galectin-9N find stable poses with specific interactions, which proposes a possible explanation to the gal/gulo 9C/9N selectivity.
Original language | English |
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Pages (from-to) | 34-39 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 11 |
Issue number | 1 |
Early online date | 2019 Dec 4 |
DOIs | |
Publication status | Published - 2020 |
Subject classification (UKÄ)
- Medicinal Chemistry
Free keywords
- epimers
- Galactose
- galectin-9
- gulose
- N-phenyl
- selectivity