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Synthesis of Multivalent Carbohydrate‐Centered Glycoclusters as Nanomolar Ligands of the Bacterial Lectin LecA from Pseudomonas aeruginosa
Author(s) -
Gening Marina L.,
Titov Denis V.,
Cecioni Samy,
Audfray Aymeric,
Gerbst Alexey G.,
Tsvetkov Yury E.,
Krylov Vadim B.,
Imberty Anne,
Nifantiev Nikolay E.,
Vidal Sébastien
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201300135
Subject(s) - lectin , chemistry , isothermal microcalorimetry , isothermal titration calorimetry , dissociation constant , biochemistry , divalent , thermostability , stereochemistry , in vitro , linker , pseudomonas aeruginosa , titration , combinatorial chemistry , enzyme , bacteria , organic chemistry , biology , receptor , physics , genetics , quantum mechanics , enthalpy , computer science , operating system
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.