Synthesis of β-galactosylamides as Ligands of the Peanut Lectin. Insights into the Recognition Process
|Author/s||Cano, María Emilia
García Moreno, M. Isabel
García Fernández, José Manuel
Uhrig, María Laura
|Department||Universidad de Sevilla. Departamento de Química orgánica|
|Abstract||The synthesis of mono and divalent β-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 ...
The synthesis of mono and divalent β-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 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.
|Funding agencies||Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Argentina
Centre national de la recherche scientifique (CNRS). France
Ministerio de Economía y Competitividad (MINECO). España
Junta de Andalucía
European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
|Project ID.||UBACyT 2013–2016 GC
|Citation||Cano, M.E., Varela, O., García Moreno, M.I., García Fernández, J.M., Kovensky, J. y Uhrig, M.L. (2017). Synthesis of β-galactosylamides as Ligands of the Peanut Lectin. Insights into the Recognition Process. Carbohydrate Research, 443-444, 58-67. https://doi.org/10.1016/j.carres.2017.03.018.|
|Synthesis of beta-galactosylam ...||1.599Mb||[PDF]||View/|