Novel copper-peptide complexes based on fragments of the amyloid beta peptide, implicated in the pathogenesis of Alzheimer's Disease, will be studied structurally and chemically. The purposes of these studies are to elucidate the role of several amino acid sequence motifs of interest found in the A-beta peptide as well as such biologically important metalloenzymes as cytochrome c oxidase, petidylglycine alpha-hydroxylating monoxygenase, and dopamine beta-hydroxygenase. The research will potentially shed light on the role of the sequences of interest on binding copper, determining structure, and activating copper for biological function in these metalloenzymes. In addition, the studies address the roles of copperdioxygen reactivity and copper-peptide interactions in the oxidative stress associated with Alzheimer's Disease and experimentally linked at A-beta. This will be accomplished by structural characterization of copper-peptide complexes in the +1 and +2 oxidation states, as well as reactivity and mechanistic studies of Cu(l) chemistry with dioxygen and hydrogen peroxide.
|Himes, Richard A; Karlin, Kenneth D (2009) Copper-dioxygen complex mediated C-H bond oxygenation: relevance for particulate methane monooxygenase (pMMO). Curr Opin Chem Biol 13:119-31|