Probing Carbohydrate-Lectin
Recognition in Heterogeneous
Environments with Monodisperse Cyclodextrin-Based Glycoclusters
- Publication date
- Publisher
Abstract
A series of β-cyclodextrin (βCD)-scaffolded
glycoclusters
exposing heterogeneous yet perfectly controlled displays of α-mannosyl
(α-Man) and β-lactosyl (β-Lact) antennas were synthesized
to probe the mutual influence of varying densities of the saccharide
motifs in the binding properties toward different plant lectins. Enzyme-linked
lectin assay (ELLA) data indicated that the presence of β-Lact
residues reinforced binding of α-Man to the mannose-specific
lectin concanavalin A (Con A) even though homogeneous β-Lact
clusters are not recognized at all by this lectin, supporting the
existence of synergic recognition mechanisms (<i>heterocluster
effect</i>). Conversely, the presence of α-Man motifs in
the heteroglycoclusters also resulted in a binding-enhancing effect
of β-Lact toward peanut agglutinin (PNA), a lectin strongly
binding multivalent lactosides but having no detectable affinity for
α-mannopyranosides, for certain architectural arrangements.
Two-site, sandwich-type ELLA data corroborated the higher lectin clustering
efficiency of heterogeneous glycoclusters compared with homogeneous
displays of the putative sugar ligand with identical valency. A turbidity
assay was also consistent with the previous observations. Most revealingly,
the lectin cross-linking ability of heterogeneous glycoclusters was
sensitive to the presence of high concentrations of the non-ligand
sugar, strongly suggesting that “mismatching” saccharide
motifs may modulate carbohydrate-lectin specific recognition in a
lectin-dependent manner when present in highly dense displays together
with the “matching” ligand, a situation frequently encountered
in biological systems