Synthesis of beta-galactosylamides as ligands of the peanut lectin. Insights into the recognition process
Résumé
The synthesis of mono and divalent beta-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from L-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from beta-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azideequipped scaffolds through the copper catalyzed azide-alkyne cycloaddition. Thus, a family of structurally related mono and divalent beta-N-galactopyranosylamides was obtained and fully characterized. The binding affinities of the ligands towards the model lectin PNA were measured by the enzyme-linked lectin assay (ELLA). The IC50 values were significantly higher than that of galactose but the presence of hydroxyl groups in the aglycone chain improved lectin recognition. Docking and molecular dynamics experiments were in accordance with the hypothesis that a hydroxyl group properly disposed in the linker could mimic the Glc O3 in the recognition process. On the other hand, divalent presentation of the ligands led to lectin affinity enhancements. (C) 2017 Elsevier Ltd. All rights reserved.