{Reference Type}: Journal Article {Title}: Recent advances in photoaffinity labeling strategies to capture Glycan-Protein interactions. {Author}: Babulic JL;De León González FV;Capicciotti CJ; {Journal}: Curr Opin Chem Biol {Volume}: 80 {Issue}: 0 {Year}: 2024 Jun 3 {Factor}: 8.972 {DOI}: 10.1016/j.cbpa.2024.102456 {Abstract}: Glycans decorate all cells and are critical mediators of cellular processes through recognition by glycan-binding proteins (GBPs). While targeting glycan-protein interactions has great therapeutic potential, these interactions are challenging to study as they are generally transient and exhibit low binding affinities. Glycan-based photo-crosslinkable probes have enabled covalent capture and identification of unknown GBP receptors and glycoconjugate ligands. Here, we review recent progress in photo-crosslinking approaches targeting glycan-mediated interactions. We discuss two prominent emerging strategies: 1) development of photo-crosslinkable oligosaccharide ligands to identify GBP receptors; and 2) cell-surface glyco-engineering to identify glycoconjugate ligands of GBPs. Overall, photoaffinity labeling affords valuable insights into complex glycan-protein networks and is poised to help elucidate the glycan-protein interactome, providing novel targets for therapeutic intervention.