Multivalent mannosides with inherent macrophage recognition abilities, built on b-cyclodextrin, RAFT cyclopeptide or peptide dendrimer cores, trigger selective inhibition of lysosomal b-glucocerebrosidase or a-mannosidase depending on valency and topology, offering new opportunities in multitargeted drug design. Multivalency is an underpinning action principle in the interaction of oligosaccharide moieties in glycoproteins and glyco-lipids with carbohydrate binding receptors (lectins) in nature. 1 The thermodynamic and kinetic advantage of multiple glyco-tope moieties interacting with many receptor sites, termed 'multivalent or cluster effect', is attributed to several possible factors that frequently act concertedly, including steric stabilization , chelate effect, secondary subsite involvement, local concentration and cross-linking effects. Reproducing this strategy with synthetic multivalent glycoligands has proven a very effective approach for advancing our understanding on the molecular mechanisms of many biological events 2 and also provides broad opportunities for therapeutic interventions. 3 The external sugar coating in such devices is generally considered to impart biocom-patibility and warrant a ''safe'' profile. Notwithstanding, recent evidence suggests that multivalency has the potential, not only to enhance the avidity towards a range of lectins sharing the same cognate sugar ligand, but also to elicit off-target inhibition of glycosidases, which may result in unforeseen promiscuity. First characterized for multimeric iminosugar-type displays, 4,5