Neighboring amide participation in the Fenton oxidation of a sulfide to sulfoxide, vinyl sulfide and ketone relevant to oxidation of methionine thioether side chains in peptides

Abstract

Oxidation of Met affects the stability of proteins, and was identified as a step in the beta amyloid-dependent pathogenesis of Alzheimer's disease. One-electron oxidation of Met is facilitated through stabilization of sulfide radical cations with electron-rich heteroatoms. The formation of such 2-center-3-electron bonds, formed between sulfide radical cations and amides, leads to pronounced product selectivity during biologically relevant oxidation conditions. Conformationally constrained methionine analogs embedded within a norbornane framework, i.e., 2,6-endo, endo-and 2,6-exo, endo-pyrrolidine amide thiomethyl bicyclo[2.2.1]heptanes