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Crosslinking Glutathionylation Mediated by O2-Arylated (Bis)diazeniumdiolate "Double JS-K"

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45



* FARE Award Winner


  • RJ Holland
  • AE Maciag
  • V Kumar
  • JE Saavedra
  • RK Prud'homme
  • H Chakrapani
  • LK Keefer


Attachment of glutathione (GSH) to cysteine residues in proteins (S-glutathionylation ) is an easily reversible post-translational modification that can profoundly alter protein structure and function. Often serving in a protective role, e.g., by temporarily saving protein thiols from irreversible oxidation and inactivation, glutathionylation is normally identified and semi-quantitatively assessed using anti-GSH antibodies thought to be specific for recognition of the S-glutathionylation modification. Here we describe an alternate mechanism of protein glutathionylation in which the sulfur atoms of the GSH and the protein’s thiol group are covalently bound via a crosslinking agent, rather than through a disulfide bond. The modification is recognized by the anti-GSH antibody as if it were authentic S-glutathionylation, requiring mass spectrometry to distinguish between them. The cross-linking pathway likely plays an important role in mediating the action of Double JS-K and related bis-diazeniumdiolates as anti-cancer agents.

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