Specific reaction of Met 35 in amyloid beta peptide with hypochlorous acid.

The reaction of the amyloid beta peptide (Abeta) with hypochlorous acid and hydroxyl radicals was analysed by spectrophotometry and mass spectrometry. N-acetylmethionine, Abeta25-35 and Abeta1-42 reacted rapidly with hypochlorous acid. The relative reaction rates of N-acetylmethionine and Abeta with hypochlorous acid was in the order N-acetylmethionine > Abeta25-35 > Abeta1-42. While the reaction of Abeta25-35 in the presence of a slight excess of hypochlorous acid resulted in complete conversion of Met35 to Met35 sulphoxide, Abeta1-42 required more than a 4-fold excess of hypochlorous acid for complete conversion of Met35. Identical products were obtained when Abeta25-35 and Abeta1-42 were treated with a hypochlorous acid generating system. Conversion of Met35 to Met35 sulphoxide in Abeta abolished the aggregation of Abeta25-35. Reaction of Abeta with hydroxyl radicals resulted in limited conversion of Met35 to Met35 sulphoxide. The specific reaction of Met35 in Abeta with hypochlorous acid to form Met35 sulphoxide has been analysed.