title: Arrest of beta-amyloid fibril formation by a pentapeptide ligand.
abstract: Polymerization of amyloid beta-peptide (Abeta) into amyloid fibrils is a critical step in the pathogenesis of Alzheimer's disease. Here, we show that peptides incorporating a short Abeta fragment (KLVFF; Abeta16-20) can bind full-length Abeta and prevent its assembly into amyloid fibrils. Through alanine substitution, it was demonstrated that amino acids Lys16, Leu17, and Phe20 are critical for binding to Abeta and inhibition of Abeta fibril formation. A mutant Abeta molecule, in which these residues had been substituted, had a markedly reduced capability of forming amyloid fibrils. The present data suggest that residues Abeta16-20 serve as a binding sequence duringA beta polymerization and fibril formation. Moreover, the present KLVFF peptide may serve as a lead compound for the development of peptide and non-peptide agents aimed at inhibiting Abeta amyloidogenesis in vivo.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Hospital, S-171 76 Stockholm, Sweden.
authors.forename: L O
authors.initials: LO
authors.lastname: Tjernberg
authors.forename: J
authors.initials: J
authors.lastname: Näslund
authors.forename: F
authors.initials: F
authors.lastname: Lindqvist
authors.forename: J
authors.initials: J
authors.lastname: Johansson
authors.forename: A R
authors.initials: AR
authors.lastname: Karlström
authors.forename: J
authors.initials: J
authors.lastname: Thyberg
authors.forename: L
authors.initials: L
authors.lastname: Terenius
authors.forename: C
authors.initials: C
authors.lastname: Nordstedt
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011108:Polymers; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D009842:Oligopeptides; D010446:Peptide Fragments; D011108:Polymers; C075222:amyloid beta-protein (1-42)