Highly regioselective deprotection of a series of 2‐amino pyranose building blocks was achieved by enzymatic hydrolysis. These monodeprotected intermediates were successfully used in the synthesis of a variety of glycoconjugate derivatives with a core of glucosamine or galactosamine, including neo‐glycoproteins and glycosphingolipids. The hydrolysis catalyzed by acetylxylan esterase from Bacillus pumilus (AXE) is suitable for the synthesis of neo‐glycoproteins with an N‐acetyl glucosamine core. The hydrolysis catalyzed by Candida rugosa lipase (CRL) was successfully applied in the preparation of new sialylated glycolipids starting from glucosamine building blocks protected as phthalimide. This chemoenzymatic approach can be used for the preparation of new glycoconjugate products with anticancer activity.

b-Cyclodextrin (b-CD) and derivatives are approved therapeutics in >30 clinical settings. b-CDs have also shown promise as therapeutics for treatment of some lysosomal storage disorders, such as Niemann-Pick disease type C, and other disease states which involve metabolite accumulation in the lysosome. In these cases, b-CD activity relies on transport to the lysosome, wherein it can bind hydrophobic substrate and effect extraction. The post-translational attachment of N-glycans terminated in mannose-6phosphate (M6P) residues is the predominant method by which lysosomal enzymes are targeted to the lysosome. In this work we covalently attach a synthetic biantennary bis-M6P-terminated N-glycan to b-CD and study the effect of the added glycans in a mammalian cell line. The formation of a host guest complex with a Cy5 fluorophore allows study of both cellular internalisation and transport to the lysosome by fluorescence microscopy. Results indicate that the rates of both internalisation and lysosomal transport are increased by the attachment of M6P-glycans to b-CD, indicating that M6P-glycan conjugation may improve the therapeutic effectiveness of b-CD for the treatment of disorders involving hydrophobic metabolite accumulation in the lysosome.The cyclodextrins 1 (CDs) are a family of cyclic oligosaccharides, comprising 6 (a-CD), 7 (b-CD), 8 (g-CD), or more, a-(1→4)linked D-glucopyranose residues. Besides numerous other uses, they have found applications in >30 clinical settings 2 as drug delivery systems, 3 taking advantage of their lipophilic central cavity to bind to hydrophobic drugs, 4 increasing their solubility, stability, and bioavailability. Chemical modification of CDs, may improve their efficacy. For example, 2-hydroxypropyl-b-CD and sulfobutylether-β-CD 5 are both clinically used as pharmaceutical excipients for poorly water-soluble drugs. The lysosomal storage disorders (LSDs) 6 are a series of >70 rare, but incurable and often fatal, genetically inherited diseases, the clinical manifestations of which arise from the build-up of undegraded lysosomal metabolites. In general, each disease is caused by the lack of a functional enzyme in the lysosome to catalyse a required degradation pathway, resulting in the gradual occupation of undegraded metabolites (also termed accumulating substances). Amongst several treatment strategies 7 that have been investigated against the LSDs, such as enzyme replacement therapy (ERT), 8 gene therapy, chaperone therapy and substrate reduction therapy, a novel emerging and complimentary strategy is reduction of the accumulated substance. In the case of Niemann-Pick disease type C, 9 the major accumulated metabolites are glycosphingolipids and unesterified cholesterol; hydrophobic guests than can be accommodated inside the cavity of b-CD, as demonstrated by the use of b-CDs to modulate the cholesterol content of plasma membranes. 10 Testing of 2-hydroxypropyl-b-CD in both murine 11 and feline disease models for Niemann-Pick type C revealed beneficial effects, 12 so that a compass...