Rational Design and Synthesis of Optimized Glycoclusters for Multivalent Lectin-Carbohydrate Interactions: Influence of the Linker Arm

Investor logo

Warning

This publication doesn't include Faculty of Education. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.
Authors

CECIONI Samy PRALY Jean-Pierre MATTHEWS Susan E WIMMEROVÁ Michaela IMBERTY Anne VIDAL Sebastien

Year of publication 2012
Type Article in Periodical
Magazine / Source Chemistry - A European Journal
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://onlinelibrary.wiley.com/doi/10.1002/chem.201200010/suppinfo
Doi http://dx.doi.org/10.1002/chem.201200010
Field Biochemistry
Keywords carbohydrates; click chemistry; glycoclusters; lectin; multivalency
Attached files
Description The design of multivalent glycoclusters requires the conjugation of biologically relevant carbohydrate epitopes functionalized with linker arms to multivalent core scaffolds. The multigram-scale syntheses of three structurally modified triethyleneglycol analogues that incorporate amide moiety(ies) and/or a phenyl ring offer convenient access to a series of carbohydrate probes with different water solubilities and rigidities. Evaluation of flexibility and determination of preferred conformations were performed by conformational analysis. Conjugation of the azido-functionalized carbohydrates with tetra-propargylated core scaffolds afforded a library of 18 tetravalent glycoclusters, in high yields, by CuI-catalyzed azidealkyne cycloaddition (CuAAC). The compounds were evaluated for their ability to bind to PA-IL (the LecA lectin from the opportunistic pathogen Pseudomonas aeruginosa). Biochemical evaluation through inhibition of hemagglutination assays (HIA), enzyme-linked lectin assays (ELLA), surface plasmon resonance (SPR), and isothermal titration microcalorimetry (ITC) revealed improved and unprecedented affinities for one of the monovalent probes (K-d=5.8 mu M) and also for a number of the tetravalent compounds that provide several new nanomolar ligands for this tetrameric lectin.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.