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Updated: Jan 16, 2026

Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines
Published on: November 25, 2017
Preparation of poly-N-(methyl)aminooxy serine polypeptides by NCA ring-opening polymerization for modification with
Francesco Palmieri1, Marlinde Waardenburg1, Justyna M Dobruchowska1
1Division of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, Utrecht 3584 CG, The Netherlands. g.j.p.h.boons@uu.nl.
Abstract:
N-Carboxyanhydride (NCA) ring-opening polymerization offers an attractive approach for the construction of polypeptides. Here, we report the synthesis of a serine NCA-functionalized monomer bearing a methylaminooxy group, enabling post-polymerization attachment of complex oligosaccharides via a neo-glycosylation reaction. It provides an attractive alternative to traditional click reactions, allowing direct conjugation of glycans with a free reducing end without requiring a reactive linker or toxic reagents. Enzymatically produced 6-sialyl lactose was efficiently conjugated to the methylaminooxy moieties of the polypeptide. The resulting neo-glycopolymer was analyzed by size-exclusion chromatography (SEC) to determine molecular weight and by diffusion-ordered spectroscopy (DOSY) nuclear magnetic resonance (NMR), which confirmed a high degree of functionalization and a substantial increase in hydrodynamic radius. Glycan attachment proceeds under mild acidic conditions highlighting the versatility of the polypeptide scaffold to yield brush-like glycosylated polypeptides.
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