Dityrosine Cross-Linked A Peptides: Fibrillar 
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- 作者：Joshua C. Yoburn ; Wenqiang Tian ; Justin O. Brower ; James S. Nowick ; Charles G. Glabe ; and David L. Van Vranken
- 刊名：Chemical Research in Toxicology
- 出版年：2003
- 出版时间：April 2003
- 年：2003
- 卷：16
- 期：4
- 页码：531 - 535
- 全文大小：91K
- 年卷期：v.16,no.4(April 2003)
- ISSN：1520-5010
文摘
Recent reports by Galeazzi and co-workers demonstrated the susceptibility of A
(1-42) toundergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formeddityrosine cross-links in A(1-40) using these enzymatic conditions as well as a copper-H2O2method. The efficiency of dityrosine cross-link formation is strongly influenced by theaggregation state of A; more dityrosine is formed when copper-H2O2 or horseradishperoxidase-catalyzed oxidation is applied to fibrillar A vs soluble A. Once formed, dityrosinecross-links are susceptible to further oxidative processes and it appears that cross-links formedin soluble A react through these pathways more readily than those formed in fibrillar A.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(8-14). Two-dimensional 1H NMR studiesof the short dityrosine dimer offer no evidence of structure. Thus, the fibrillar structure of Aenhances formation of dityrosine cross-links, but dityrosine cross-links do not seem to enhancelocal secondary structure.
(1-42) toundergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formeddityrosine cross-links in A(1-40) using these enzymatic conditions as well as a copper-H2O2method. The efficiency of dityrosine cross-link formation is strongly influenced by theaggregation state of A; more dityrosine is formed when copper-H2O2 or horseradishperoxidase-catalyzed oxidation is applied to fibrillar A vs soluble A. Once formed, dityrosinecross-links are susceptible to further oxidative processes and it appears that cross-links formedin soluble A react through these pathways more readily than those formed in fibrillar A.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(8-14). Two-dimensional 1H NMR studiesof the short dityrosine dimer offer no evidence of structure. Thus, the fibrillar structure of Aenhances formation of dityrosine cross-links, but dityrosine cross-links do not seem to enhancelocal secondary structure.