title: Effect of D-amino acids at Asp23 and Ser26 residues on the conformational preference of Abeta20-29 peptides.
abstract: The effects of d-amino acids at Asp(23) and Ser(26) residues on the conformational preference of beta-amyloid (Abeta) peptide fragment (Abeta(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 Abeta(20-29), [d-Asp(23)]Abeta(20-29), and [d-Ser(26)]Abeta(20-29) peptides under different conditions, the spectra were measured in 10mM acetate buffer (pH 3) and in 2,2,2-trifluoroethanol (TFE). The spectroscopic results indicated that at pH 3, Abeta(20-29) peptide takes random coil with beta-turn structure, while [d-Ser(26)]Abeta(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)]Abeta(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, Abeta(20-29), [d-Asp(23)]Abeta(20-29), and [d-Ser(26)]Abeta(20-29) peptides adopt 3(10)-helix, alpha-helix, and random coil with some beta-turn structures, respectively. The VCD data obtained for the Abeta 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 Abeta peptides studied here. This observation suggests that dehydration can have a significant influence on the structural preferences of these peptides.
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Shanmugam
authors.forename: Prasad L
authors.initials: PL
authors.lastname: Polavarapu
authors.forename: Balázs
authors.initials: B
authors.lastname: Hallgas
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Majer
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry*; D002942:Circular Dichroism; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012694:Serine / Q000737:chemistry*; D012996:Solutions
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012996:Solutions; D001224:Aspartic Acid; D012694:Serine