Targeted Delivery of Fluorescent High-Mannose-Type Oligosaccharide Cathepsin Inhibitor Conjugates

Three fluorescent cathepsin inhibitor glycoconjugates have been designed, synthesized, and evaluated in terms of their cell internalization and cathepsin inhibitory properties. The conjugates are composed of a peptide epoxysuccinate, capable of covalent and irreversible binding to cysteine proteases, coupled to a fluorescent BODIPY dye and functionalized with a mono-, tri-, or heptamannoside. Mannose-receptor-dependent uptake of the probes in live dendritic cells is shown to depend on the type of carbohydrate attached. Where uptake of the monomannoside is poor and mannose-receptor-independent, the intracellular labeling of cathepsins by the probes equipped with a tri- or heptamannoside conjugate appeared concentration- and mannose-receptor-dependent.