Chemoenzymatic Synthesis of a Phosphorylated Glycoprotein.
Angew Chem Int Ed Engl
; 55(16): 5058-61, 2016 Apr 11.
Article
em En
| MEDLINE
| ID: mdl-26971709
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-ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Nova Zelândia