Sialic acid-containing glycoproteins are important players in cancer metastasis and viral infections, yet there hasn’t been a method for their complete analysis on cell surfaces. To address that problem, Ronghu Wu and coworkers at Georgia Institute of Technology have developed a method that combines metabolic labeling, chemical modification, and mass spectrometric proteomics (Chem. Sci. 2015, DOI: 10.1039/c5sc01124h). First the researchers use metabolic labeling to incorporate an azido group into sialoglycoproteins. They next add a biotin affinity tag to the azido group via a copper-free click chemistry reaction that’s mild enough to be carried out on live cells. Then they use an avidin probe to enrich the biotin-tagged sialoglycoproteins for mass spectrometric proteomic analysis. The Georgia Tech team used the method to identify 395 sialoglycosylation sites on 213 surface proteins from human kidney cancer cells. They also analyzed two breast cancer cell lines, one that is highly invasive and one that is not. The sialoglycopeptides were more abundant in the invasive breast cancer cells than in the noninvasive cells.