Synthesis of Physiological Relevant Amyloid-β Cross-linked Peptide Dimers — ASN Events
  1. Schedule
  2. Session 2 SPPS Methodology I
  3. Synthesis of Physiological Relevant Amyloid-β Cross-linked Peptide Dimers

Synthesis of Physiological Relevant Amyloid-β Cross-linked Peptide Dimers (#5)

Jade M. Cottam 1 2 , W. Mei Kok 1 2 3 , Giuseppe D. Ciccotosto 2 3 4 , John A. Karas 2 , Denis B. Scanlon 1 2 , Kevin J. Barnham 2 4 5 , Craig A. Hutton 1 2
  1. School of Chemistry, The University of Melbourne, Parkville, VIC, Australia
  2. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
  3. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
  4. Mental Health Research Institute, Parkville, VIC, Australia
  5. Department of Pharmacology, The University of Melbourne, Parkville, VIC, Australia

The involvement of β-amyloid (Aβ) peptides in the progression of Alzheimer's disease (AD) is widely accepted. However the precise role that Aβ plays in AD is yet to be elucidated. Strong evidence suggests that the soluble oligomers of Aβ are the neurotoxic species.1  In particular, dityrosine cross-linked Aβ dimers are proposed to be the physiologically relevant Aβ species linked to the progression of AD.2  However, to date no efficient method has been reported to prepare such species. We present here the first chemical synthesis of these physiologically relevant cross-linked Aβ dimers.3,4   We demonstrate the nature of the cross-link dramatically affects the biophysical properties of the dimers. These dityrosine cross-linked Aβ dimers showed increased toxicity in a neuronal cell-line assay compared with their corresponding monomers.4

  1. Cleary, J. P.; Walsh, D. M.; Hofmeister, J. J.; Shankar, G. M.; Kuskowski, M. A.; Selkoe, D. J.; Ashe, K. H. Nat Neurosci 2005, 8, 79.
  2. Barnham, K. J.; Haeffner, F.; Ciccotosto, G. D.; Curtain, C. C.; Tew, D.; Mavros, C.; Beyreuther, K.; Carrington, D.; Masters, C. L.; Cherny, R. A.; Cappai, R.; Bush, A. I. The FASEB Journal 2004.
  3. Kok, W. M.; Scanlon, D. B.; Karas, J. A.; Miles, L. A.; Tew, D. J.; Parker, M. W.; Barnham, K. J.; Hutton, C. A. Chemical Communications 2009, 6228.
  4. Kok, W. M.; Cottam, J. M.; Ciccotosto, G. D.; Miles, L. A.; Karas, J. A.; Scanlon, D. B.; Roberts, B. R.; Parker, M. W.; Cappai, R.; Barnham, K. J.; Hutton, C. A., submitted manuscript