Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The majority of lysosomal enzymes are targeted to the lysosome by post-translational tagging with N-glycans terminating in mannose-6-phosphate (M6P) residues. Some current enzyme replacement therapies (ERTs) for lysosomal storage disorders are limited in their efficacy by the extent to which the recombinant enzymes bear the M6P-terminated glycans required for effective trafficking. Chemical synthesis was combined with endo-β-N-acetylglucosaminidase (ENGase) catalysis to allow the convergent synthesis of glycosyl amino acids bearing M6P residues. This approach can be extended to the remodeling of proteins, as exemplified by RNase. The powerful synergy of chemical synthesis and ENGase-mediated biocatalysis enabled the first synthesis of a glycoprotein bearing M6P-terminated N-glycans in which the glycans are attached to the peptide backbone by entirely natural linkages.

Original publication

DOI

10.1002/anie.201600817

Type

Journal article

Journal

Angew Chem Int Ed Engl

Publication Date

11/04/2016

Volume

55

Pages

5058 - 5061

Keywords

ENGase, N-glycans, carbohydrates, glycoproteins, mannose-6-phosphate, Acetylglucosaminidase, Carbohydrate Sequence, Glycoproteins, Phosphorylation