N-Azidoacetylmannosamine and N-Azidoacetylgalactosamine Incorporation into N-Glycans of Recombinantly Expressed Human Lactotransferrin by Metabolic Oligosaccharide Engineering

Abstract

Over the past years the application of therapeutic and diagnostic proteins such as antibodies or hormones has had a substantial impact on modern medicine. Many of these agents are glycoproteins with conjugated oligosaccharide chains. The introduction of chemically modified monosaccharides into glycan structures of such proteins provides an excellent option to modify their efficacy, affinity, and tolerance. Here we demonstrate the efficient introduction of azido-modified N-acetylmannosamine and N-acetylgalactosamine into glycans of the promising protein therapeutic candidate lactotransferrin (LTF).

Keywords:

• N-azidoacetylgalactosamine
• N-azidoacetylmannosamine
• Click chemistry
• Recombinant glycoprotein
• Lactotransferrin
• Metabolic oligosaccharide engineering

ACKNOWLEGEMENTS

This work was supported by a grant to S.H. of the program “Arbeitsgruppenwettbewerb Glykobiotechnologie” of the Bundesministerium für Bildung und Forschung. C.P.R.H. acknowledges financial support from the Deutsche Forschungsgemeinschaft (Emmy Noether grant HA 4468/2-1), the SFB 765, and the Boehringer-Ingelheim Foundation (Plus 3 Perspektivenprogramm). Further support by the Europäischer Fonds für regionale Entwicklung (S.H.) is acknowledged.