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

Abstract

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].