title: Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process.
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 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 IC50values 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.
authors.affiliation: Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Pabellón 2, Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Centro de Investigación en Hidratos de Carbono (CIHIDECAR), Buenos Aires, Argentina.
authors.forename: María Emilia
authors.initials: ME
authors.lastname: Cano
authors.affiliation: Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Pabellón 2, Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Centro de Investigación en Hidratos de Carbono (CIHIDECAR), Buenos Aires, Argentina.
authors.forename: Oscar
authors.initials: O
authors.lastname: Varela
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, c/ Profesor García González 1, 41012, Sevilla, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: García-Moreno
authors.affiliation: Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, Avda. Américo Vespucio 49, 41092, Sevilla, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García Fernández
authors.affiliation: Laboratoire de Glycochimie, des Antimicrobiens et des Agroressources (LG2A)-CNRS UMR 7378, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens Cedex, France.
authors.forename: José
authors.initials: J
authors.lastname: Kovensky
authors.affiliation: Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Pabellón 2, Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA, Centro de Investigación en Hidratos de Carbono (CIHIDECAR), Buenos Aires, Argentina. Electronic address: mluhrig@qo.fcen.uba.ar.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Uhrig
mesh_terms: D005690:Galactose / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D019887:Peanut Agglutinin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D008024:Ligands; D019887:Peanut Agglutinin; D005690:Galactose
keywords: Divalent ligands; ELLA assay; Molecular dynamics; Peanut agglutinin; β-galactosylamides