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Cell-specific bioorthogonal tagging of glycoproteins

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-022-33854-0

2041-1723

Anna Cioce, Beatriz de la Calle, Tatiana Rizou, Sarah Lowery, Victoria L. Bridgeman, Keira E. Mahoney, Andrea Marchesi, Ganka Bineva‐Todd, Helen R. Flynn, Zhen Li, Ömür Y. Tastan, Chloë Roustan, Pablo Soro-Barrio, Mahmoud‐Reza Rafiee, Acely Garza-Garcı́a, Aristotelis Antonopoulos, Thomas M. Wood, Tessa Keenan, Peter Both, Kun Huang, Fabio Parmeggian, Ambrosius P. Snijders, Mark Skehel, Svend Kjær, Martin A. Fascione, Carolyn R. Bertozzi, Stuart M. Haslam, Sabine L. Flitsch, Stacy A. Malaker, Ilaria Malanchi, Benjamin Schumann,

Click Chemistry and Applications

Abstract Altered glycoprotein expression is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines. More complex co-culture models usually rely on sorting procedures for proteome analyses and rarely capture the details of protein glycosylation. Here, we report a strategy termed Bio-Orthogonal Cell line-specific Tagging of Glycoproteins (BOCTAG). Cells are equipped by transfection with an artificial biosynthetic pathway that transforms bioorthogonally tagged sugars into the corresponding nucleotide-sugars. Only transfected cells incorporate bioorthogonal tags into glycoproteins in the presence of non-transfected cells. We employ BOCTAG as an imaging technique and to annotate cell-specific glycosylation sites in mass spectrometry-glycoproteomics. We demonstrate application in co-culture and mouse models, allowing for profiling of the glycoproteome as an important modulator of cellular function.