title: Polyalanine-based peptides as models for self-associated beta-pleated-sheet complexes.
abstract: The occurrence of beta-sheet motifs in a number of neurodegenerative disorders has brought about the need for the de novo design of soluble model beta-sheet complexes. Such model complexes are expected to further the understanding of the interconversion processes that occur from cellular allowed random coil or alpha-helical conformation into insoluble cell-deleterious beta-pleated-sheet motifs. In the present study, polyalanine-based peptides (i.e., derived from Ac-KA14K-NH2) were designed that underwent conformational changes from monomeric random coil conformations into soluble, macromolecular beta-pleated-sheet complexes without any covalent modification. The interconversion was found to be length-, environment-, and concentration-dependent and to be driven by hydrophobic interactions between the methyl groups of the alanine side chains. A series of substitution analogs of Ac-KA14K-NH2 was used to study the amino acid acceptability within the hydrophobic core of the complex, as well as at both termini. The formation of amyloid plaques in a number of amyloidogenic peptides could be related to the presence of amino acids within their sequences that were found to have a high propensity to occur in these model beta-sheet complexes.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Blondelle
authors.forename: B
authors.initials: B
authors.lastname: Forood
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
authors.forename: E
authors.initials: E
authors.lastname: Pérez-Payá
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004355:Drug Stability; D006358:Hot Temperature; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D046911:Macromolecular Substances; D010455:Peptides; C019529:polyalanine