Structural, kinetic and cytotoxicity aspects of 12-28 β-amyloid protein fragment: a reappraisal

A chemical, structural and biological study on the β‐amyloid peptide β12–28 is reported which was carried out in order to assess the feasibility using this peptide fragment as a model of the natural β‐amyloid protein. The aggregation properties of β12–28 have been investigated by pulse field‐gradient NMR spectroscopy, Fourier transform infrared spectroscopy and transmission electron microscopy. The results obtained suggest that β12–28 behaviour is comparable to that of the natural β‐amyloid protein although kinetically slower. Translational diffusion coefficients obtained by NMR on an aged β12–28 solution suggest that the soluble peptide fraction is composed of oligomeric intermediates adopting an extended ellipsoidal assembly rather than a spherical one. The β12–28 peptide proved to be cytotoxic in PC12 cell cultures as monitored by the MTT assay, although a lack of reproducibility was observed in the dose‐response experiments. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.