We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Chemoenzymatic Synthesis of a Phosphorylated Glycoprotein.
- Authors
Priyanka, Pragya; Parsons, Thomas B.; Miller, Antonia; Platt, Frances M.; Fairbanks, Antony J.
- Abstract
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.
- Subjects
CHEMICAL synthesis; GLYCOPROTEINS; LYSOSOMAL storage diseases; CATALYSIS; LYSOSOMES
- Publication
Angewandte Chemie International Edition, 2016, Vol 55, Issue 16, p5058
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201600817