ArticleJACS Au2025
Oxidative and Hydrolytic HNO Formation from a Clinical Drug Hydroxyurea Catalyzed by Horseradish Peroxidase: Basic Mechanism, Active Site Effect, and Implications for Drug Design.
Article in JACS Au, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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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Who cites it
2 citing papers in PubMed.
- Real-time photoactivated SRS imaging enables spatiotemporally controlled nitroxyl release and therapeutic guidance in vivo.Nature communications · 2026Article
- Oxidative HNO Formation Mechanisms from NHACS omega · 2025Article
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Authors and funding
4 authors.
Funding
Abstract
HNO plays an important role in many biological processes related to vasodilation, regulation of enzyme activities, and neurological functions. The understanding of enzymatic oxidative HNO-releasing pathways in biology remains scarce. We investigated HNO formation from a well-established small-molecule drug hydroxyurea catalyzed by horseradish peroxidase (HRP). Density functional theory results reveal two sequential proton-coupled electron transfers from hydroxyurea to HRP Compound I as the most favorable mechanism for HNO generation, which was found to be kinetically feasible and thermodynamically favorable. This is consistent with its experimentally observed reactivity. Moreover, the large active site model study uncovered interesting conformation changes involving HRP's amino acid H-bonding network through the reaction pathway, which were employed to anchor the evolving substrate via its key CONH
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