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Chemoenzymatic Synthesis of a Phosphorylated Glycoprotein
Author(s) -
Priyanka Pragya,
Parsons Thomas B.,
Miller Antonia,
Platt Frances M.,
Fairbanks Antony J.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201600817
Subject(s) - glycan , biochemistry , glycoprotein , chemistry , lysosome , enzyme , mannose , biocatalysis , rnase p , mannose 6 phosphate receptor , phosphorylation , peptide , glycosylation , recombinant dna , catalysis , gene , rna , ionic liquid
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.