biostudies-literatureZhang QSmall Business Innovation ResearchNational Institute of General Medical SciencesSchool of Medicine, Emory UniversityNIGMS NIH HHS16750-16757https://www.ebi.ac.uk/biostudies/studies/S-EPMC11503514biostudies-literatureUnknown96(42)N-glycosylation is a critical post-translational modification involved in various biosynthetic pathways and disease mechanisms. In this study, we present an optimized oxidative release of natural glycans (ORNG) method using household bleach that enables the rapid and efficient release of N-glycans from biological samples. We thoroughly investigated the ORNG mechanism, identifying key intermediates and side products and providing valuable insights into the oxidative release process. The method is highly efficient, releasing a wide range of N-glycans, including high-mannose, hybrid, and complex structures, with minimal sample processing. Our ORNG-based specific N-glycan profiling approach has demonstrated high sensitivity and efficiency, particularly in releasing N-glycans resistant to enzymAnalytical chemistryOxidative Release of Natural Glycans: Unraveling the Mechanism for Rapid N-Glycan Glycomics Analysis.PMC11503514R01 GM137011R44 GM133252SCR_023524R01GM137011R44GM133252Lasanajak YSong XZhang QfalseOxidative Release of Natural Glycans: Unraveling the Mechanism for Rapid N-Glycan Glycomics Analysis.N-glycosylation is a critical post-translational modification involved in various biosynthetic pathways and disease mechanisms. In this study, we present an optimized oxidative release of natural glycans (ORNG) method using household bleach that enables the rapid and efficient release of N-glycans from biological samples. We thoroughly investigated the ORNG mechanism, identifying key intermediates and side products and providing valuable insights into the oxidative release process. The method is highly efficient, releasing a wide range of N-glycans, including high-mannose, hybrid, and complex structures, with minimal sample processing. Our ORNG-based specific N-glycan profiling approach has demonstrated high sensitivity and efficiency, particularly in releasing N-glycans resistant to enzym2024-01-01T00:00:00Z2024 Oct2026-06-03T00:16:41.725Z2025-04-04T01:24:44.047ZS-EPMC115035143938748910.1021/acs.analchem.4c03246