Dityrosine cross-linked Aβ peptides:: Fibrillar β-structure in Aβ(1-40) is conducive to formation of dityrosine cross-links but a dityrosine cross-link in αβ(8-14) does not induce β-structure

Recent reports by Galeazzi and co-workers demonstrated the susceptibility of Abeta(1-42) to undergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formed dityrosine cross-links in Abeta(1-40) using these enzymatic conditions as well as a copper-H2O2 method. The efficiency of dityrosine cross-link formation is strongly influenced by the aggregation state of Abeta; more dityrosine is formed when copper-H2O2 or horseradish peroxidase-catalyzed oxidation is applied to fibrillar Abeta vs soluble Abeta. Once formed, dityrosine cross-links are susceptible to further oxidative processes and it appears that cross-links formed in soluble Abeta react through these pathways more readily than those formed in fibrillar Abeta. Because preorganization of fibrils affects the efficiency of dityrosine formation, we examined the effect of dityrosine formation upon local peptide conformation by assessing the solution structure of a small dityrosine dimer derived from Abeta(8-14). Two-dimensional H-1 NMR studies of the short dityrosine dimer offer no evidence of structure. Thus, the fibrillar structure of Abeta enhances formation of dityrosine cross-links, but dityrosine cross-links do not seem to enhance local secondary structure.