Journal
CHEMBIOCHEM
Volume 11, Issue 10, Pages 1430-1442Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201000167
Keywords
carbohydrates; click chemistry; lectins; linkers; molecular dynamics
Funding
- Centre National de la Recherche Scientifique
- Ministere Delegue a l'Enseignement Superieur et a la Recherche
- Conseil Regional de Picardie
Ask authors/readers for more resources
Multimeric lactosides based on carbohydrate scaffolds with valencies ranging from 1 to 4 and different linker lengths were synthesized by a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The binding affinities and crosslinking abilities of the new click clusters toward biologically relevant galectins (gal-1, gal-3) and peanut lectin were evaluated by fluorescent polarization assay (FPA) and enzyme-linked lectin assay (ELLA), respectively. FPA indicated that the binding affinities of the synthetic multilactosides towards the galectins increased proportionally with their lactosyl content, without significant differences due to the spacer length. ELLA evidenced a modest cluster effect for the multivalent conjugates, with a relative potency per lactoside ranging from 2.1 to 3.2. Nearly identical binding affinities were recorded for derivatives differing in the length of the linkers, in agreement with the FPA data. These results demonstrate that this parameter does not significantly influence the recognition process when interactions occur at a single lectin site. Molecular dynamics revealed that glycoconjugates adopt a pseudoglobular structure with a random localization of the lactoside residues. These spatial distributions were observed irrespective of the linker length; this explains the virtually equal affinities recorded by ELLA. In contrast, two-site sandwich ELLA clearly revealed that multivalent derivatives bearing the longest spacers were more efficient for crosslinking lectins. Intrinsic affinities, devoid of aggregation effects, and crosslinking capabilities are, therefore, not directly related phenomena that must be taking into consideration in neoglycoconjugate design for specific applications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available