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Pyrone and pyranthione scaffolds for click-to-release and biological gas delivery

  • Stony Brook University

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Click-to-release chemistry provides methods to control molecular activation in biological systems using bioorthogonal reactions. Here, we discuss several classical click-to-release reactions, including Staudinger-Bertozzi-based cleavage systems, 1,3-dipolar cycloaddition-based cleavable systems, and tetrazine-triggered inverse-electron-demand Diels-Alder (IEDDA) cleavage systems. We describe in detail pyrone and pyranthione scaffolds that undergo IEDDA reactions with endo-bicyclo[6.1.0]nonyne (endo-BCN), resulting in the release of carbon dioxide or carbonyl sulfide, with the latter converted to hydrogen sulfide by carbonic anhydrase. We discuss approaches to evaluate the kinetics and bioorthogonality of a pyrone compound library. Finally, we discuss protein labeling, quantitative analysis of hydrogen sulfide release, and mitochondrial hydrogen sulfide imaging in live HeLa cells.

Original languageEnglish
Title of host publicationBioorthogonal Labeling
EditorsAdam R. Urbach
PublisherAcademic Press Inc.
Pages427-461
Number of pages35
ISBN (Print)9780443432248
DOIs
StatePublished - Jan 2026

Publication series

NameMethods in Enzymology
Volume731
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • Bioorthogonal chemistry
  • Click-to-release
  • Gasotransmitters
  • Hydrogen sulfide
  • Inverse-electron-demand Diels-Alder (IEDDA)
  • Pyranthiones
  • Pyrones

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