Chemical Reporter for Visualizing Metabolic Cross-Talk between Carbohydrate Metabolism and Protein Modification

Metabolic
chemical reporters have been largely used to study posttranslational
modifications. Generally, it was assumed that these reporters entered
one biosynthetic pathway, resulting in labeling of one type of modification.
However, because they are metabolized by cells before their addition
onto proteins, metabolic chemical reporters potentially provide a
unique opportunity to read-out on both modifications of interest and
cellular metabolism. We report here the development of a metabolic
chemical reporter 1-deoxy-N-pentynyl glucosamine
(1-deoxy-GlcNAlk). This small-molecule cannot be incorporated into
glycans; however, treatment of mammalian cells results in labeling
of a variety proteins and enables their visualization and identification.
Competition of this labeling with sodium acetate and an acetyltransferase
inhibitor suggests that 1-deoxy-GlcNAlk can enter the protein acetylation
pathway. These results demonstrate that metabolic chemical reporters
have the potential to isolate and potentially discover cross-talk
between metabolic pathways in living cells.