Dityrosine cross-linked Abeta peptides: fibrillar beta-structure in Abeta(1-40) is conducive to formation of dityrosine cross-links but a dityrosine cross-link in Abeta(8-14) does not induce beta-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-H(2)O(2) method. The eff...

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Veröffentlicht in:Chemical research in toxicology 2003-04, Vol.16 (4), p.531-535
Hauptverfasser: Yoburn, Joshua C, Tian, Wenqiang, Brower, Justin O, Nowick, James S, Glabe, Charles G, Van Vranken, David L
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Sprache:eng
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Zusammenfassung: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-H(2)O(2) method. The efficiency of dityrosine cross-link formation is strongly influenced by the aggregation state of Abeta; more dityrosine is formed when copper-H(2)O(2) 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 (1)H 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.
ISSN:0893-228X