Achieving cell-type selectivity in metabolic oligosaccharide engineering

Metabolic oligosaccharide engineering (MOE) is a transformative technology, enabling the chemical labeling and subsequent analysis of glycans. Central to this method are monosaccharide analogs, termed metabolic chemical reporters (MCRs), that contain abiotic functional groups that can undergo an increasing number of bioorthogonal reactions. Typically, these abiotic groups were designed to be as small as possible, allowing them to be tolerated by metabolic enzymes and glycosyltransferases that transform MCRs into donor sugars and add them into glycans, respectively. This generality allows MCRs to be used by a variety of cells and tissues but can also be a limitation in their application to investigate glycosylation of specific cell-types in multicellular systems. Here, we review different methods that are beginning to transition MCRs into cell selective tools, with the potential to increase the already large impact these compounds have had on glycoscience.