AMYLOID BETA-PEPTIDE SPIN-TRAPPING .2. EVIDENCE FOR DECOMPOSITION OF THE PBN SPIN ADDUCT

SYNTHETIC beta-amyloid peptides (A beta s) react with the spin trap phenyl-tert-butyl nitrone (PBN) to form products detectable by electron paramagnetic resonance (EPR) spectroscopy. At least two EPR-detectable products can be distinguished from the A beta/PBN reaction, and peptide toxicity towards glutamine synthetase enzyme correlates with the type of PBN reaction product observed. We have reacted synthetic A beta(25-35) peptide with [C-12]- or [C-13]PBN to demonstrate that the two products represent alternate pathways of spin adduct decomposition. Results indicate that the C=N bond of PBN is cleaved by A beta in what we hypothesize is a radical addition-fragmentation reaction.