title: Synthesis of multivalent carbohydrate-centered glycoclusters as nanomolar ligands of the bacterial lectin LecA from Pseudomonas aeruginosa.
abstract: A family of fifteen glycoclusters based on a cyclic oligo-(1→6)-β-D-glucosamine core has been designed as potential inhibitors of the bacterial lectin LecA with various valencies (from 2 to 4) and linkers. Evaluation of their binding properties towards LecA has been performed by a combination of hemagglutination inhibition assays (HIA), enzyme-linked lectin assays (ELLA), and isothermal titration microcalorimetry (ITC). Divalent ligands displayed dissociation constants in the sub-micromolar range and tetravalent ligands displayed low nanomolar affinities for this lectin. The influence of the linker could also be demonstrated; aromatic moieties are the best scaffolds for binding to the lectin. The affinities observed in vitro were then correlated with molecular models to rationalize the possible binding modes of these glycoclusters with the bacterial lectin.
authors.affiliation: Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow, Russia.
authors.forename: Marina L
authors.initials: ML
authors.lastname: Gening
authors.forename: Denis V
authors.initials: DV
authors.lastname: Titov
authors.forename: Samy
authors.initials: S
authors.lastname: Cecioni
authors.forename: Aymeric
authors.initials: A
authors.lastname: Audfray
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Gerbst
authors.forename: Yury E
authors.initials: YE
authors.lastname: Tsvetkov
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Krylov
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vidal
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000737:chemistry*
chemical_list: D018829:Adhesins, Bacterial; D006001:Glycoconjugates; C102929:LecA protein, bacteria; D008024:Ligands; D005944:Glucosamine
keywords: Pseudomonas aeruginosa; click chemistry; glucosamines; glycocluster; lectins; oligosaccharides