TOXI 96 |
| Protein and peptide modifications caused by oxidative stress are believed to play an important role in the degenerative diseases of aging such as Alzheimer's disease. We have previously demonstrated that oxidative modifications occur on amyloid beta peptide at His-13/His-14 and that they may be potential biomarkers of Alzheimer's disease. Here we report a novel oxidative modification at the N-terminus of amyloid beta peptides. Amyloid beta 1-40 or truncated forms containing the amino terminus were incubated with Cu(II) and ascorbic acid in Tris buffer (pH 7.4). Analysis of the products by liquid chromatography-tandem mass spectrometry using a linear ion trap revealed that a novel modification had occurred by oxidative decarboxylation at Asp-1 followed by pyruvate formation through deamination (-45 Da). This was confirmed by formation of a methoxime derivative as a mixture of syn and anti-isomers from reaction of the pyruvate derivative with hydroxylamine hydrochloride. Supported by NIH grant R01CA95586. |
|
Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster
Sci-Mix
Division of Chemical Toxicology |