Recent reports by Galeazzi and co-workers demonstrated the susceptibility of A
![](/images/gifchars/beta2.gif)
(1-42) toundergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formeddityrosine cross-links in A
![](/images/gifchars/beta2.gif)
(1-40) using these enzymatic conditions as well as a copper-H
2O
2method. The efficiency of dityrosine cross-link formation is strongly influenced by theaggregation state of A
![](/images/gifchars/beta2.gif)
; more dityrosine is formed when copper-H
2O
2 or horseradishperoxidase-catalyzed oxidation is applied to fibrillar A
![](/images/gifchars/beta2.gif)
vs soluble A
![](/images/gifchars/beta2.gif)
. Once formed, dityrosinecross-links are susceptible to further oxidative processes and it appears that cross-links formedin soluble A
![](/images/gifchars/beta2.gif)
react through these pathways more readily than those formed in fibrillar A
![](/images/gifchars/beta2.gif)
.Because preorganization of fibrils affects the efficiency of dityrosine formation, we examinedthe effect of dityrosine formation upon local peptide conformation by assessing the solutionstructure of a small dityrosine dimer derived from A
![](/images/gifchars/beta2.gif)
(8-14). Two-dimensional
1H NMR studiesof the short dityrosine dimer offer no evidence of structure. Thus, the fibrillar structure of A
![](/images/gifchars/beta2.gif)
enhances formation of dityrosine cross-links, but dityrosine cross-links do not seem to enhancelocal secondary structure.