Amyloid-like Misfolding Of Peptides By Membrane Mimicking Environments

Sodium dodecyl sulfate has been proven as an amyloid-like misfolding agent [1-3]. Our study comprises the biophysical characterization of human peptides in the presence of submicellar and micellar concentrations of SDS. The prodynorphin derived peptides (Big dynorphin, dynorphin A and dynorphin B) [4], the amyloid β peptide [5], and the proinsulin derived C-peptide are our subject of study. As determined by CD and FTIR spectroscopy, the peptide structural transitions involve different secondary structures, such as random coil, β-sheet and α-helix. By means of NMR, dynamic light scattering, native-PAGE or ThT fluorescence, we have shown that all the peptides transit through a high molecular weight aggregated state at submicellar detergent concentrations. Finally, studies with model membranes with different charge composition have been carried out to relate the structural characterization of these peptides to their possible role in the cell and their action mechanisms in pathology.1. Rangachari, V., Moore, B.D., Reed, D.K., Sonoda, L.K., Bridges, A.W., Conboy, E., Hartigan, D., and Rosenberry, T.L. (2007). Biochemistry 46, 12451-12462.2. Rangachari, V., Reed, D.K., Moore, B.D., and Rosenberry, T.L. (2006). Biochemistry 45, 8639-8648.3. Tew, D.J., Bottomley, S.P., Smith, D.P., Ciccotosto, G.D., Babon, J., Hinds, M.G., Masters, C.L., Cappai, R., and Barnham, K.J. (2008). Biophys J 94, 2752-2766.4. Hugonin, L., Barth, A., Graslund, A., and Peralvarez-Marin, A. (2008). Biochim Biophys Acta. in press.5. Wahlstrom, A., Hugonin, L., Peralvarez-Marin, A., Jarvet, J., and Graslund, A. (2008). FEBS J. in press.