Reporting in Nature Chemical Biology, Ngo et al. describe a system for cell-selective protein labelling in mixtures of cells (J. T. Ngo et al. Nature Chem. Biol. doi:10.1038/nchembio.200; 2009). Their work is based on the principle that proteins can be tracked in experiments if they are engineered so that some of their constituent amino acids contain a tag, such as a radioactive label; tagged amino acids can be added to cells in culture, whereupon the cells incorporate them into newly formed proteins. The general problem with this approach is that all the cells in the culture become labelled, whereas it might be that only certain types of cell need to be tagged.
Ngo and colleagues' solution to that problem involves non-naturally occurring amino acids that contain azide (N3) groups in their side chains. Azides don't react with biological molecules, but under certain conditions they do react quickly with synthetic molecules that contain alkyne groups (which have carbon–carbon triple bonds). Once incorporated into proteins, azide-containing amino-acid residues will thus react with alkyne-containing fluorescent dyes or affinity reagents, so tagging the proteins for imaging, detection or separation.
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