Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom.
Bioconjug Chem. 2022 Aug 17;33(8):1467-1473. doi: 10.1021/acs.bioconjchem.2c00169. Epub 2022 Jul 25.
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 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 AcManNCyoc, 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. AcManNCyoc gave better labeling than the azido-tagged AcManNAz and has significant potential for and imaging of glycosylated cancer biomarkers.
甲基环丙烯基（Cyoc）标记的四乙酰化单糖，特别是甘露胺衍生物，是使用代谢寡糖工程和极快的逆电子需求 Diels-Alder 生物正交反应进行癌症医学成像的有前途的工具。然而，由于这些单糖衍生物的水溶性低，其潜力尚未得到充分探索。为了解决这个问题，我们试图改变 Cyoc 标记的单糖的乙酰化程度，并探讨其对各种癌细胞系中聚糖标记程度的影响。我们证明，在 AcManNCyoc 的情况下，三乙酰化和二乙酰化衍生物的细胞标记程度明显高于四乙酰化单糖。相比之下，对于更易溶解的叠氮化物标记的糖，乙酰化程度的降低导致聚糖标记程度降低。AcManNCyoc 的标记效果优于叠氮化物标记的 AcManNAz，并且对糖基化癌症生物标志物的成像具有重要潜力。
