Multivalency Effects in Protein−Carbohydrate Interaction:  The Binding of the Shiga-like Toxin 1 Binding Subunit to Multivalent C-Linked Glycopeptides

Abstract

A series of monovalent and bivalent glycopeptides displaying a C-linked analogue of the Pk trisaccharide, the in vivo ligand for the pentavalent Shiga-like toxin binding subunit (SLT-1B), were prepared and evaluated as ligands for SLT-1B by isothermal titration microcalorimetry and competitive enzyme-linked immunosorbent assay (ELISA). Although none of the monovalent ligands showed any enhancement in affinity compared to O-methyl glycoside, two bivalent ligands show significant enhancements in affinity in assays. This observation represents the first calorimetric observation of an enhancement in affinity for this system. In contrast, only one of the two ligands shows an enhancement in the competitive ELISA. Together, these data signal a difference in the means by which the two ligands achieve affinity, apparently triggered by a change in the nature of the linker domain. These results provide a rationalization for apparently contradictory reports from the recent literature and again emphasize the importance of investigating complex binding phenomena by multiple techniques.

Globotriose‐Functionalized Gold Nanoparticles as Multivalent Probes for Shiga‐like Toxin

“…[17] Toone et al developed bivalent C-linked P k -trisaccharide-based glycopeptides as affinity ligands for B-Slt in microcalorimetry studies. [18] Inhibition of BSlt binding to cells has been demonstrated to protect mice from infection by E. coli O157:H7. [19] Thus, it could be of great benefit to develop both a B-Slt antagonist to protect against E. coli infection, and a sensitive, accurate and rapid assay to detect the toxin.…”

Inhibition of Alzheimer amyloid β aggregation by polyvalent trehalose

“…Many groups have reported the multivalent effect and the generation of the multivalent compounds such as glycopeptides [14], glycocalixarenes [15], glycodendrimers [16], and glycopolymers [17]. In particular, glycopolymers carrying a saccharide at the side chain exhibit a large multivalent effect and applicability as biomaterials.…”

Synthesis of Lactose Dendrimers and Multivalency Effects in Binding to the Cholera Toxin B Subunit

“…These provided evidence for different binding mechanisms, including bridging between toxin pentamers, depending on the nature of the spacer. [27] An interesting mix of chelation of binding sites within a single toxin and bridging between toxin molecules has been observed for the Shiga-like toxin with a multivalent molecule containing ten ligands. [9a] In a competitive ELISA assay, this dodecavalent system was seven orders of magnitude more effective than monovalent reference compounds.…”