biostudies-literatureUnknownWu YHEver-increasing evidence confirms the role of O-GlcNAcase (OGA) in mediating cell growth and development as well as pathology and underscores the importance of developing sensitive and selective chemical tools for the study of OGA biology. Here, based on our previously developed protein-encapsulation strategy, we designed and synthesized a series of fluorogenic probes based on resorufin, and assembled their composites with human serum albumin (HSA) for the selective detection of endogenous OGA activity in live cells. We show that host-guest self-assembly with HSA significantly enhances the OGA sensitivity of the probes in aqueous solution and cells. The structure of the complex of a glycoprobe and HSA was resolved by small-angle X-ray scattering. We demonstrate that the replacement of the Chemical sciencehttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12910607biostudies-literatureProtein-encapsulated fluorogenic probes for the selective detection of endogenous O-GlcNAcase (OGA).PMC12910607Li JYe ZRGuo CHu XLJames TDWu YHHe XPfalseProtein-encapsulated fluorogenic probes for the selective detection of endogenous O-GlcNAcase (OGA).Ever-increasing evidence confirms the role of O-GlcNAcase (OGA) in mediating cell growth and development as well as pathology and underscores the importance of developing sensitive and selective chemical tools for the study of OGA biology. Here, based on our previously developed protein-encapsulation strategy, we designed and synthesized a series of fluorogenic probes based on resorufin, and assembled their composites with human serum albumin (HSA) for the selective detection of endogenous OGA activity in live cells. We show that host-guest self-assembly with HSA significantly enhances the OGA sensitivity of the probes in aqueous solution and cells. The structure of the complex of a glycoprobe and HSA was resolved by small-angle X-ray scattering. We demonstrate that the replacement of the 2026-01-01T00:00:00Z2026 Feb2026-07-16T04:59:17.057Z2026-07-09T13:10:08.078ZS-EPMC129106074171020610.1039/d5sc06843f