Metabolic Glycan Labeling of Cancer Cells Using Variably Acetylated Monosaccharides

• Published in: Bioconjugate chemistry Vol. 33; no. 8; pp. 1467 - 1473
• Main Authors: Parle, Daniel R., Bulat, Flaviu, Fouad, Shahd, Zecchini, Heather, Brindle, Kevin M., Neves, André A., Leeper, Finian J.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17.08.2022
• Subjects: Acetylation; Biomarkers; Cancer; Glycan; Labeling; Medical imaging; Metabolic engineering; Monosaccharides; Monosaccharides - metabolism; Neoplasms - diagnostic imaging; Oligosaccharides; Polysaccharides - metabolism; Staining and Labeling - methods; Sugar; Tumor cell lines
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.2c00169

Methylcyclopropene (Cyoc)-tagged tetra-acetylated monosaccharides, and in particular mannosamine derivatives, are promising tools for medical imaging of cancer using metabolic oligosaccharide engineering and the extremely fast inverse electron-demand Diels–Alder bioorthogonal reaction. However, the in vivo potential of these monosaccharide derivatives has yet to be fully explored due to their low aqueous solubility. To address this issue, we sought to vary the extent of acetylation of Cyoc-tagged monosaccharides and probe its effect on the extent of glycan labeling in various cancer cell lines. We demonstrate that, in the case of Ac x ManNCyoc, tri- and diacetylated derivatives generated significantly enhanced cell labeling compared to the tetra-acetylated monosaccharide. In contrast, for the more readily soluble azide-tagged sugars, a decrease in acetylation led to decreased glycan labeling. Ac3ManNCyoc gave better labeling than the azido-tagged Ac4ManNAz and has significant potential for in vitro and in vivo imaging of glycosylated cancer biomarkers.