Cross-linked Tyrosine Derivatives in Peptides and Proteins
We are developing novel methods for the preparation of cross-linked tyrosine derivatives, such as dityrosine, trityrosine and pulcherosine. In addition to their presence in small peptides, the formation of these tyrosine derivatives in proteins has been associated with a variety of diseases and disorders, including Alzheimer’s and Parkinson’s diseases. We are investigating the relationship between oxidatively cross-linked Aβ peptide oligomers and the progression of Alzheimer’s disease (in collaboration with Assoc Prof Kevin Barnham, Dept of Pathology and Bio21 Institute).
W. M. Kok, J. M. Cottam, G. D. Ciccotosto, L. A. Miles, J. A. Karas, D. B. Scanlon, B. R. Roberts, M. W. Parker, R. Cappai, K. J. Barnham and C. A. Hutton, “Synthetic Dityrosine-linked β-Amyloid Dimers Form Stable, Soluble, Neurotoxic Oligomers,” Chem. Sci. 2013, 4, 4449–4454.
S. C. Drew, W. M. Kok, C. A. Hutton and K. J. Barnham, “Cu2+ Coordination of Covalently Cross-linked β-Amyloid Dimers,” Appl. Mag. Res. 2013, 44, 927–939.
V. L. Villemagne, K. A. Perez, K. E. Pike, W. M. Kok, C. C. Rowe, A. R. White, P. Bourgeat, O. Salvado, J. Bedo, C. A. Hutton, N. G. Faux, C. L. Masters, K. J. Barnham, “Blood-borne Amyloid-β dimer correlates with clinical markers of Alzheimer’s disease,” J. Neurosci., 2010, 30, 6315–6322.
W. M. Kok, D. B. Scanlon, J. A. Karas, D. Tew, L. A. Miles. M. W. Parker, K. J. Barnham and C. A. Hutton, “Solid Phase Synthesis of Homodimeric Peptides: Preparation of Covalently Linked Dimers of Amyloid-beta Peptide,” Chem. Commun., 2009, 6228–6230.
O. Skaff, K. A. Jolliffe and C. A. Hutton, “Synthesis of the side-chain cross-linked tyrosine oligomers dityrosine, trityrosine and pulcherosine,” J. Org. Chem., 2005, 70, 7353–7363.
- Congratulations Mohammad! April 24, 2017
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