In recent years, many metalloproteases have drawn attention because of their capability to degrade β-amyloid peptides and they are currently studied as pharmacological targets for Alzheimer's disease (AD). We have recently shown that the activity of insulin-degrading enzyme (IDE), but not of neprilysin, could be differently modulated by metal ions, proposing that the binding of the latter to the catalytic site could be responsible for such peculiar behavior [1-3]. Here, we have synthesized peptides that mimic the different amino acidic sequences of the various catalytic sites. The binding of such peptides with zinc (II) and copper(II) has been investigated by thermodynamic and spectroscopic techniques. At physiological pH, results show that the thermodynamic stability of complexes with copper(II) are different for the different consensus sequences investigated. Moreover, some results regarding the effect of metal ions on the degradation of amylin by IDE will also be discussed. Acknowledgements Financial support from FIRB MERIT Prot. RBNE08HWLZ and MIUR FIRB-ItalNanoNet RBPR05JH2P_021 is acknowledged. References  G. Grasso, F. Salomone, G. R. Tundo, G. Pappalardo, C. Ciaccio, G. Spoto, A. Pietropaolo, M. Coletta, E. Rizzarelli J Inorg Biochem 2012, 117, 351.  G. Grasso, A. Pietropaolo, G. Spoto, G. Pappalardo, G. R. Tundo, C. Ciaccio, M. Coletta, E. Rizzarelli Chemistry-A European Journal 2011, 17, 2752.  G. Grasso, M. L. Giuffrida, E. Rizzarelli Metallomics 2012, 4, 937.
|Titolo:||Metalloproteases and metal ions in Alzheimer’s disease: recent findings|
|Data di pubblicazione:||2013|
|Appare nelle tipologie:||4.1 Contributo in Atti di convegno|