Tetravalent glycocyclopeptide with nanomolar affinity to wheat germ agglutinin

Abstract

A series of tetravalent glycocyclopeptides functionalized with GlcNAc was synthesized using copper(I)-catalysed alkyne–azide cycloaddition, oxime ligation and thiol–ene coupling. The binding ability of these compounds towards wheat germ agglutinin was studied by a competitive ELLA test and ITC experiments. While all compounds were able to inhibit WGA binding to GlcNAc-polymer coated surfaces at low concentrations, derivative 17 having an aliphatic spacer and thioether linkage was 4.9 × 10⁶ times more potent on a per sugar basis than GlcNAc. This remarkably strong effect was confirmed by ITC experiments as these revealed an association constant of 9 nM for this compound, therefore presenting a gain of 200 000 times over GlcNAc. These results for compound 17 represent the highest binding properties reported for WGA.