Carbohydrate moieties on glycosylated small molecules play specific roles that attenuate their biological activities. In addition to their influence on physicochemical properties, sugar residues often serve as handles that mediate binding interactions between the small molecule and its target, and underpin their associated activity. Glycosylated natural products epitomize this phenomenon, where the sugars on macrolide antibiotics are illustrative. The producer of the bacterial translation inhibitor methymycin, for example, adopts a pro-drug strategy using a glucose moiety (Fig. ). When glucose is attached to the desosamine residue of the macrolide, the compound does not fit into the binding site in the ribosome exit tunnel.