Book of Abstracts - Ruhr-Universität Bochum

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ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Synthesis of Ferrocene Peptide Conjugates and their Application as Inhibitors of
Peptide Association
Samaneh Beheshti, a and Heinz-Bernhard Kraatz a
a The University of Western Ontario, Faculty of Science, Department of Chemistry, 1151 Richmond St,
N6A 5B7, London, Ontario, Canada. Email: sbehesh@uwo.ca
The amyloid beta peptide (Aβ) with 40-42 amino acids is the major constituent of plaques found in
the brain of people affected with Alzheimer’s disease. 1 There is a hypothesis that conformational
switching from α-helical to β-sheet ultimately leads to amyloid fibril formation . On this basis, finding
compounds that are able to destabilize the β-sheet structure and to interfere with the assembly of
peptide strands is a useful strategy to prevent peptide aggregation and fibril formation. Synthetic
peptides have been reported as β-sheet breakers that preclude amyloid formation. 2 For example, a
novel pentapeptide inhibitor that has a proline in place of valine and an aspartic acid in place of
alanine in the Aβ17-21 (Leu-Val-Phe-Phe-Ala) fragment has been reported with the ability to inhibit the
formation of amyloid fibrils. 3 In this work, a series of Fc-peptide conjugates is prepared of the type
FcCO-Val-Phe-Phe-OR (1:R = Me, 2:R = H), Fc[CO-Val-Phe-Phe-OR]2 (3:R = Me, 4:R = H), Fc[CO-
Val-Phe-OR]2 (5:R = Me, 6:R = H) and Fc[CO-Leu-Val-OR]2 (7:R = Me, 8:R = H) . Conformational
properties of these ferrocene peptide conjugates and their interaction with several sequences of Aβ
have been studied in solution by circular dichroism and scanning electron microscopy. In addition, the
interaction of Aβ attached on the gold surface with these ferrocene peptide conjugates has been
studied by using electrochemical methods.
References
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Nordstedt, J. Biol. Chem. 1996, 271, 8545-8548.
2. C. Soto, E.M. Sigurdsson, L. Morelli, R.A. Kumar, E.M. Castano, B. Frangione, Nat. Med. 1998, 4,
822-826.
3. C. Adessi, M.J. Frossard, C. Boissard, S. Fraga, S. Bieler, T. Ruckle,F. Vilbois, S.M. Robinson, M.
Mutters, W.A. Banks, C. Soto, J. Biol. Chem. 2003, 278, 13905-13911.
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