A synthetic approach to 'click' neoglycoprotein analogues of EPO employing one-pot native chemical ligation and CuAAC chemistry.
Chem Sci
; 10(3): 815-828, 2019 Jan 21.
Article
em En
| MEDLINE
| ID: mdl-30774876
ABSTRACT
The clinical significance of batch-wise variability on the pharmacokinetics and potency of commercial erythropoietin (EPO), prepared recombinantly as a heterogeneous mixture of glycoforms, necessitates the development of synthetic strategies to afford homogenous EPO formulations. Herein we present a previously unexplored and divergent route towards 'click' neoglycoprotein analogues of EPO, employing one-pot native chemical ligation (NCL) of alkynylated peptides and copper-catalysed azide-alkyne cycloaddition (CuAAC) with azido monosaccharides. By design, our synthetic platform permits glycosylation at virtually any stage, providing flexibility for the synthesis of various glycoforms for biological analysis. Insights obtained from attempted folding of our 'click' neoglycoprotein EPO analogue, bearing four different neutral sugar moieties, highlight the important role played by the charged oligosaccharides present in native EPO glycoproteins.
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01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Chem Sci
Ano de publicação:
2019
Tipo de documento:
Article