Multivalent Gold Glycoclusters: High Affinity Molecular Recognition by Bacterial Lectin PA‐IL

Abstract

Multivalent protein-carbohydrate interactions are involved in the initial stages of many fundamental biological and pathological processes through lectin-carbohydrate binding. The design of high affinity ligands is therefore necessary to study, inhibit and control the processes governed through carbohydrate recognition by their lectin receptors. Carbohydrate-functionalised gold nanoclusters (glyconanoparticles, GNPs) show promising potential as multivalent tools for studies in fundamental glycobiology research as well as biomedical applications. Here we present the synthesis and characterisation of galactose functionalised GNPs and their effectiveness as binding partners for PA-IL lectin from Pseudomonas aeruginosa. Interactions were evaluated by hemagglutination inhibition (HIA), surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) assays. Results show that the gold nanoparticle platform displays a significant cluster glycoside effect for presenting carbohydrate ligands with almost a 3000-fold increase in binding compared with a monovalent reference probe in free solution. The most effective GNP exhibited a dissociation constant (K(d)) of 50 nM per monosaccharide, the most effective ligand of PA-IL measured to date; another demonstration of the potential of glyco-nanotechnology towards multivalent tools and potent anti-adhesives for the prevention of pathogen invasion. The influence of ligand presentation density on their recognition by protein receptors is also demonstrated.

Mannose-centered aromatic galactoclusters inhibit the biofilm formation of Pseudomonas aeruginosa

“…16 Inhibition of LecA with synthetic ligands can be achieved with high affinity oligogalactosylated ligands. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] High binding can be obtained thanks to the so called glycoside cluster effect. 32,33 The design of multivalent ligands targeting LecA has been recently reviewed.…”

Studies of Highly-Ordered Heterodiantennary Mannose/Glucose-Functionalized Polymers and Concanavalin A Protein Interactions Using Isothermal Titration Calorimetry

“…24-26 To date, neoglycopolymers (a polymer scaffold with incorporated carbohydrate residues) have illustrated great promise in studying GBP-governed processes. This is likely due to the ability to vary the length of the polymer chain, length and flexibility of the carbohydrate-polymerizable linker, and individual spacing of the pendant carbohydrate moieties.…”

Revisiting 30 years of biofunctionalization and surface chemistry of inorganic nanoparticles for nanomedicine

“…In the last 10 years, Penades and co-workers have extensively reported a pioneer integration of a glyconanotechnology strategy based on the use of nanoparticles to study and evaluate carbohydrate–carbohydrate, carbohydrate–protein interactions (Figure 7) (de la Fuente et al, 2001, 2006; Barrientos et al, 2003; de la Fuente and Penades, 2004, 2006), which could be used as potential tools in anti-adhesive therapy (Rojo et al, 2004), for cell–cell adhesion studies (de la Fuente et al, 2005), prevention of pathogen invasion (Reynolds et al, 2012) and for exploring blood–brain barrier permeability via neuropeptide conjugation (Frigell et al, 2014). …”