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 (PrP[Ac-106-126-NH2]) and 106-114 (PrP[Ac-106-114-NH2]) 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 PrP[Ac-106-126-NH2] and PrP[Ac-106-114-NH2] were investigated using CD and NMR spectroscopy. CD results showed that PrP[Ac-106-126-NH2] 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 PrP[Ac-106-114-NH2] fragment showed similar propensities when investigated under the same experimental conditions as those employed for PrP[Ac-106-126-NH2]. From CD experiments at different SDS concentrations, an alpha-helix/beta-sheet conformational transition was only observed in the blocked PrP[Ac-106-126-NH2] sequence. The NMR analysis confirmed the helical nature of PrP[Ac-106-126-NH2] in the presence of SDS micelles. The shorter PrP[Ac-106-114-NH2] 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 PrP [Ac-106-126-NH2].