The effects of D-amino acids at Asp(23) and Ser(26) residues on the conformational preference of beta-amyloid (A beta) peptide fragment (A beta(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 A beta(20-29), [D-Asp(23)]A beta(20-29), and [D-Ser(26)]A beta(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, A beta(20-29) peptide takes random coil with beta-turn structure, while [D-Ser(26)]A beta(20-29) peptide adopts significant amount of polyproline II (PPII) type structure along with beta-turn contribution and D-Asp-substituted peptide ([D-Asp(23)]A beta(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, A beta(20-29), [D-Asp(23)]A beta(20-29), and [D-Ser(26)]A beta(20-29) peptides adopt 3(10)-helix, alpha-helix, and random coil with some beta-turn structures, respectively. The VCD data obtained for the A beta 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 A beta peptides studied here. This observation suggests that dehydration can have a significant influence on the structural preferences of these peptides. (C) 2005 Elsevier Inc. All rights reserved.