Synthesis of Galactoclusters by Metal-Free Thiol "Click Chemistry" and Their Binding Affinities for Pseudomonas aeruginosa Lectin LecA

Mannose‐centered galactoclusters specific for lectin I of Pseudomonas aeruginosa (LecA) were synthesised by a combination of phosphoramidite chemistry and metal‐free thiol click chemistry (i.e., thiol addition to acrylamide or nucleophilic displacement of bromine in a bromoacetamide group by a thiol function). These thiol click reactions were performed with microwave assistance in the presence of Et3N and with use of a reducing agent to avoid disulfide formation. Nine tetravalent galactoclusters containing different linkers (aliphatic, oligoethyleneglycol or aromatic) were synthesised with a DNA tag. Their binding to LecA was monitored in a DNA‐based glycoarray and compared with that of a galactocluster synthesised by copper‐catalyzed azide–alkyne cycloaddition. The results indicated stronger binding of all galactoclusters relative to the monovalent galactoside but slightly weaker binding than that shown by the galactocluster incorporating a triazole ring, due to a favourable interaction of the latter with proline 51 of LecA. Galactocluster oligonucleotide conjugates were synthesised by a combination of nucleic acid chemistry and metal‐free thiol reactions (i.e., thiol Michael‐type addition or nucleophilic displacement of bromoacetamide group by a thiol). Their binding to LecA was studied with a DNA‐based microarray.