Polyalanine-based peptides as models for self-associated β-pleated- sheet complexes
Article
Blondelle, SE, Forood, B, Houghten, RA et al. (1997). Polyalanine-based peptides as models for self-associated β-pleated- sheet complexes
. BIOCHEMISTRY, 36(27), 8393-8400. 10.1021/bi963015b
Blondelle, SE, Forood, B, Houghten, RA et al. (1997). Polyalanine-based peptides as models for self-associated β-pleated- sheet complexes
. BIOCHEMISTRY, 36(27), 8393-8400. 10.1021/bi963015b
The occurrence of β-sheet motifs in a number of neurodegenerative disorders has brought about the need for the de novo design of soluble model β-sheet complexes. Such model complexes are expected to further the understanding of the interconversion processes that occur from cellular allowed random coil or α-helical conformation into insoluble cell- deleterious β-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 β-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 β-sheet complexes.
