Lysosomal storage diseases (LSDs) are a group of about 70 rare inherited diseases, characterized by metabolic disorders that result from the accumulation of large molecules within cells. This accumulation is due to the defection of critical enzymes suitable for the digestion of the large molecules. The majority of these lysosomal enzymes are delivered to the lysosome by the recognition of N-glycans terminating in mannose-6-phosphate (M6P) residues. Enzyme replacement therapy (ERT) is one of the few medical treatments for some LSDs. However some current ERTs for lysosomal storage disorders are limited in their efficacy by the lack of M6P-terminated glycans required for the effective trafficking to the lysosome on the recombinant enzyme. The chemical synthesis of M6P tagged oxazolines combined with endo-β-Nacetylglucosaminidase (ENGase) catalysis allows the convergent synthesis of glycoprotein endowed of M6P residues. The combination of these two techniques can be an optimal solution to overcome the issues of the current treatments. The synthesis of different M6P tagged oligosaccharides was achieved producing two possible donor substrates for ENGase-mediated biocatalysis glycosylation, in order to produce enzymes linked to M6P tagged residues recognisable by lysosomal receptors. It has been demonstrated that b-cyclodextrin (b-CD) can trespass the phospholipidic barrier, reach the lysosomes and bind retinal lipofuscin accumulated in cell lysosomes of subjects affected by Stargardt’s disease. In order to potentially better target bcyclodextrin to the lysosomes, one of the M6P-oligosaccharide synthesized during this project was linked to the b-CD, using 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP) as a reagent to convert the M6P-oligosaccharide into the corresponding azide derivative and eventually click the newly formed azide to the bcyclodextrin functionalised with an alkyne group exploiting the copper(I)-catalysed 1,3-dipolar cycloaddition. Fluorescence microscopy studies were eventually performed to demonstrate the ability of the M6P labelled b-CD to exploit the interaction with the cation independent mannose-6-phosphate receptor (CI-MPR) for its cellular endocytosis.