Comparative analysis of photocatalytic, enzymatic, and chemical approaches to identify canonical and noncanonical surfaceomes.

Five photocatalytic surfaceomics strategies identify numerous noncanonical cell surface proteins, revealing potential new drug targets, with high concordance across methods.

• Why it matters: The cell surface proteome is a small, critical subset of the human proteome that is underexplored for therapeutic targeting, especially noncanonical proteins lacking traditional features.
• What they did: Researchers developed and compared five photocatalytic surfaceomics techniques using Eosin Y to label cell surface proteins without cellular engineering, alongside three established methods, to analyze surfaceome composition.
• The result: All methods broadly enriched canonical surface proteins but differed in attachment mechanisms, consistently identifying many nonglycosylated, noncanonical proteins that may serve as novel drug targets.