Effect of d-amino acids at Asp 23 and Ser 26 residues on the conformational preference of Aβ 20–29 peptides

Abstract

The effects of d-amino acids at Asp 23 and Ser 26 residues on the conformational preference of β-amyloid (Aβ) peptide fragment (Aβ 20–29) have been studied using different spectroscopic techniques, namely vibrational circular dichroism (VCD), vibrational absorption, and electronic circular dichroism. To study the structure of the Aβ 20–29, [ d-Asp 23]Aβ 20–29, and [ d-Ser 26]Aβ 20–29 peptides under different conditions, the spectra were measured in 10 mM acetate buffer (pH 3) and in 2,2,2-trifluoroethanol (TFE). The spectroscopic results indicated that at pH 3, Aβ 20–29 peptide takes random coil with β-turn structure, while [ d-Ser 26]Aβ 20–29 peptide adopts significant amount of polyproline II (PPII) type structure along with β-turn contribution and d-Asp-substituted peptide ([ d-Asp 23]Aβ 20–29) adopts predominantly PPII type structure. The increased propensity for PPII conformation upon d-amino acid substitution, in acidic medium, has important biological implications. In TFE, Aβ 20–29, [ d-Asp 23]Aβ 20–29, and [ d-Ser 26]Aβ 20–29 peptides adopt 3 10-helix, α-helix, and random coil with some β-turn structures, respectively. The VCD data obtained for the Aβ peptide films suggested that the secondary structures for the peptide films are not the same as those for corresponding solution and are also different among the Aβ peptides studied here. This observation suggests that dehydration can have a significant influence on the structural preferences of these peptides.