Conformational properties of peptide fragments homologous to the 106-114 and 106-126 residues of the human prion protein: a CD and NMR spectroscopic study

Two peptide fragments, corresponding to the amino acid residues 106-126 (PrPAc-106-126-NH(2)]) and 106-114 (PrPAc-106-114-NH(2)]) of the human prion protein have been synthesised in the acetylated and amide form at their N- and C-termini, respectively. The conformational preferences of PrPAc-106-126-NH(2)] and PrPAc-106-114-NH(2)] were investigated using CD and NMR spectroscopy. CD results showed that PrPAc-106-126-NH(2)] mainly adopts an alpha-helical conformation in TFE-water mixture and in SDS micelles, while a predominantly random structure is observed in aqueous solution. The shorter PrPAc-106-114-NH(2)] fragment showed similar propensities when investigated under the same experimental conditions as those employed for PrPAc-106-126-NH(2)]. From CD experiments at different SDS concentrations, an alpha-helix/beta-sheet conformational transition was only observed in the blocked PrPAc-106-126-NH(2)] sequence. The NMR analysis confirmed the helical nature of PrPAc-106-126-NH(2)] in the presence of SDS micelles. The shorter PrPAc-106-114-NH(2)] manifested a similar behaviour. The results as a whole suggest that both hydrophobic effects and electrostatic interactions play a significant role in the formation and stabilisation of ordered secondary structures in PrPAc-106-126-NH(2)].