Selective Oxidation of N-Glycolylneuraminic Acid Using an Engineered Galactose Oxidase Variant
| Autor: | William R. Birmingham, Sabine L. Flitsch, Juana Elizabeth Reyes Martinez, Fabio Parmeggiani, Nico Kress, Josef Voglmeir, Nicholas J. Turner, Kun Huang, Ashley P. Mattey, Peter Both, Gregory S Bulmer, Jolanda M. van Munster |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
glycoprotein
010405 organic chemistry fungi food and beverages General Chemistry galactose oxidase Neu5Gc 010402 general chemistry Ligand (biochemistry) 01 natural sciences selective oxidation Catalysis 0104 chemical sciences protein modification chemistry.chemical_compound chemistry Biochemistry N-Glycolylneuraminic acid Galactose oxidase Red meat |
| Zdroj: | Mattey, A, Birmingham, W R, Both, P, Kress, N, Huang, K, Van Munster, J M, Bulmer, G, Parmeggiani, F, Voglmeir, J, Reyes Martinez, J E, Turner, N J & Flitsch, S L 2019, ' Selective Oxidation of N-Glycolylneuraminic Acid Using an Engineered Galactose Oxidase Variant ', ACS Catalysis, vol. 9, no. 9, pp. 8208-8212 . https://doi.org/10.1021/acscatal.9b02873 |
| DOI: | 10.1021/acscatal.9b02873 |
| Popis: | N-Glycolylneuraminic acid (Neu5Gc) is a common cell surface ligand in animals which is not biosynthesized in humans but can be acquired in human tissue from dietary sources such as red meat. It is important to understand the relevance of this potentially immunogenic glycan on human health, and selective detection methods are needed that can distinguish Neu5Gc from its biosynthetic precursor common in humans, i.e. N-acetylneuraminic acid (Neu5Ac). Here, we demonstrate that Neu5Gc can be selectively oxidized by an engineered variant of galactose oxidase without any reaction towards Neu5Ac. Oxidation of Neu5Gc itself allowed for the full spectroscopic characterization of the aldehyde product. In addition, we show that Neu5Gc is also oxidized when part of a typical animal oligosaccharide motif and when attached to a protein-linked N-glycan. Oxidation of Neu5Gc introduces bioorthogonal functionality that can be exclusively labeled. We demonstrate that in combination with sialidase mediated hydrolysis, this two-enzyme system can provide a useful tool for the selective detection of Neu5Gc in complex biological samples such as the biopharmaceutical alpha acid glycoprotein. |
| Databáze: | OpenAIRE |
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