Synthesis of Dodecavalent Fullerene‐Based Glycoclusters and Evaluation of Their Binding Properties towards a Bacterial Lectin

Abstract Multivalency is playing a major role in biological processes and particularly in lectin–carbohydrate interactions. The design of high‐affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide–alkyne “click” chemistry was applied to the synthesis of dodecavalent fullerene‐based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis‐fullerene adduct or glycoside). PA‐IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA‐IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme‐linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant “glycoside cluster effect” with up to a 12 000‐fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene‐based glycocluster, albeit with some differences depending on the analytical technique.