Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process. (18th April 2017)

• Record Type: Journal Article
• Authors: Cano, María Emilia; Varela, Oscar; García-Moreno, María Isabel; García Fernández, José Manuel; Kovensky, José; Uhrig, María Laura
• Is Part Of: Carbohydrate research. Volume 443/444(2017)
• Page Start: 58
• Page End: 67
• Publication Date: 2017-04-18
• Subjects: Peanut agglutinin -- β-galactosylamides -- Divalent ligands -- ELLA assay -- Molecular dynamics; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2017.03.018
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: The synthesis of mono and divalent β-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived froml -tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from β-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azide-equipped scaffolds through the copper catalyzed azide-alkyne cycloaddition. Thus, a family of structurally related mono and divalent β- 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. Graphical abstract: Highlights: β-Galactosylamine was coupled to L-tartaric anhydride as a precursor of a hydroxylated linker. An analogous succinimidyl β-galactosylamine moiety was synthesized for comparative purposes. Mono and divalent ligands were synthesized by click chemistry. The affinity of the compounds obtained for the PNA lectin was determined by ELLA. Docking and molecular dynamics calculations were in agreement with affinities observed.