Protein-encapsulated fluorogenic probes for the selective detection of endogenous O-GlcNAcase (OGA).

Yuan-Hao Wu, Chen Guo, Zi-Ru Ye, Xi-Le Hu, Tony D James, Jia Li, Xiao-Peng He

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Article in Chemical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Yuan-Hao WuKey Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology 130 Meilong Rd Shanghai 200237 China xphe@ecust.edu.cn.

Chen GuoKey Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology 130 Meilong Rd Shanghai 200237 China xphe@ecust.edu.cn.

Zi-Ru YeKey Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology 130 Meilong Rd Shanghai 200237 China xphe@ecust.edu.cn.

Xi-Le HuKey Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology 130 Meilong Rd Shanghai 200237 China xphe@ecust.edu.cn.ORCID https://orcid.org/0000-0002-8893-5673

Tony D JamesDepartment of Chemistry, University of Bath Bath BA2 7AY UK t.d.james@bath.ac.uk.ORCID https://orcid.org/0000-0002-4095-2191

Jia LiNational Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences Shanghai 201203 China jli@simm.ac.cn.ORCID https://orcid.org/0000-0003-3224-001X

Xiao-Peng HeKey Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology 130 Meilong Rd Shanghai 200237 China xphe@ecust.edu.cn.ORCID https://orcid.org/0000-0002-8736-3511

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 acetyl group in GlcNAc with a propionyl group results in selectivity for OGA over hexosaminidases (HEX) that unselectively hydrolyze hexosamines. This allows us to differentiate between two cell lines with different endogenous OGA and HEX expression levels, and selectively detect OGA activity in live cells.

Identifiers

PMID41710206

DOI10.1039/d5sc06843f

PMCPMC12910607

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