Triphenyl Phosphonium (TPP)-Derived Protein Sulfenic Acid Trapping Agents: Synthesis, Reactivity and Effect on Mitochondrial Function

Redox mediated protein modifications control numerous processes in both normal and disease metabolism. Protein sulfenic acids, formed from the oxidation of protein cysteine residues, play a critical role in thiol-based redox signaling. The reactivity of protein sulfenic acids requires their identification through chemical trapping and this paper describes the use of the triphenyl phosphonium ion to direct known sulfenic acid traps to the mitochondria, a verified source of cellular reactive oxygen species. Coupling of the triphenyl phosphonium (TPP) group with the 2, 4-(dioxocyclohexyl)propoxy (DCP) unit and the bicyclo[6.1.0]nonyne (BCN) group produces two new probes, DCP-TPP and BCN-TPP. DCP-TPP and BCN-TPP react with C165A AhpC-SOH, a model protein sulfenic acid, to form the expected adducts with second order rate constants of k = 1.1 M-1 s-1 and k = 5.99 M-1 s-1, respectively as determined by electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS). The TPP group does not alter the rate of...