Surface Density of Ligands Controls In‐Plane and Aggregative Modes of Multivalent Glycovesicle‐Lectin Recognitions

Abstract

Glycovesicles are ideal tools to delineate finer mechanisms of the interactions at the biological cell membranes. Multivalency forms the basis which, in turn, should surpass more than one mechanism in order to maintain multiple roles that the ligand‐lectin interactions encounter. Ligand densities hold a prime control to attenuate the interactions. In the present study, mannose trisaccharide interacting with a cognate receptor, namely, Con A, is assessed at the vesicle surface. Synthetic (1→3)(1→6)‐branched mannose trisaccharides tethered with a diacetylene monomer and glycovesicles of varying sugar densities were prepared. The polydiacetylene vesicles were prepared by maintaining uniform lipid concentrations. The interactions of the glycovesicles with the lectin were probed through dynamic light scattering and UV‐Vis spectroscopy techniques. Binding efficacies were assessed by surface plasmon resonance. Aggregative and in‐plane modes of interactions show ligand‐density dependence at the vesicle surface. Vesicles with sparsely populated ligands engage lectin in an aggregative mode (trans‐), leading to a cross‐linked complex formation. Whereas glycovesicles embedded with dense ligands engage lectin interaction in an in‐plane mode intramolecularly (cis‐). Sub‐nanomolar dissociation constants govern the intramolecular interaction occurring within the plane of the vesicle, and are more efficacious than the aggregative intermolecular interactions.

Synthetic approaches of carbohydrate based self-assembling systems

“…Yadav et al synthesized glycovesicles prepared from diacetylene-containing glycolipid, as shown in Scheme 38. 124 Pentacosadiynoic acid (PCDA) 257 was converted to diacetylene lipids 258 and 259 by amide formation. The manno-triose headgroup 260 was coupled with the diacetylene lipid 259 through an alpha-glycoside linkage to afford the glycolipid 261 .…”