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-NH 2]) and 106–114 (PrP[Ac-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 PrP[Ac-106–126-NH 2] and PrP[Ac-106–114-NH 2] were investigated using CD and NMR spectroscopy. CD results showed that PrP[Ac-106–126-NH 2] mainly adopts an α-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-NH 2] fragment showed similar propensities when investigated under the same experimental conditions as those employed for PrP[Ac-106–126-NH 2]. From CD experiments at different SDS concentrations, an α-helix/β-sheet conformational transition was only observed in the blocked PrP[Ac-106–126-NH 2] sequence. The NMR analysis confirmed the helical nature of PrP[Ac-106–126-NH 2] in the presence of SDS micelles. The shorter PrP[Ac-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 PrP[Ac-106–126-NH 2].