ReviewCurrent opinion in chemical biology2026
Chemical biology tools for the O-GlcNAc modification: Determining systems-level functions and druggability.
Review in Current opinion in chemical biology, 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
How can a single monosaccharide control nearly every human cellular feature? This question has hounded the O-GlcNAc field since 1984. Despite identifying thousands of O-GlcNAc proteins, high-throughput datasets have only deepened the mystery. This Current Opinion highlights chemical biology tools (current as of 2023-2026) that reveal coordinated O-GlcNAc networks in physiology and disease. We review five areas: (1) systems-level maps of tissue-specific OGT interactomes and substrates; (2) spatiotemporal tools for precise glycosylation manipulation; (3) multiplexed detection assays for O-GlcNAc activities alongside other PTMs; (4) targeted modulation via nontraditional inhibitors, noncatalytic OGT scaffolding, and ligand-directed assembly; and (5) disease models uncovering tissue-specific effects. Recent OGA inhibitor clinical challenges in Phase 1 and 2 studies pose existential questions about drugging O-GlcNAc, but recent advances covered in this Opinion propose insights for safe therapeutic targeting. Through the lens of new chemical biology tools, we see detailed patterns in how nutrient-responsive O-GlcNAcylation subtly regulates cellular decision-making.
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