title: Surface plasmon resonance characterization of specific binding of polyglutamine aggregation inhibitors to the expanded polyglutamine stretch.
abstract: Proteins with an abnormally expanded polyglutamine (polyQ) stretch are prone to change their conformations, leading to their aggregation, and cause inherited neurodegenerative diseases called the polyQ diseases. Although screening for polyQ aggregation inhibitors has been extensively performed, many common false-positive hits have been identified so far. In this study, we employed surface plasmon resonance (SPR) to characterize the binding specificities and affinities of polyQ aggregation inhibitors to the expanded polyQ stretch. SPR successfully detected specific binding of polyQ binding peptide 1 (QBP1) to the expanded polyQ stretch (K(d)=5.7 microM), and non-specific binding of Congo red to polyQ proteins independent of their polyQ-length. Binding affinities of polyQ aggregation inhibitors to the expanded polyQ stretch were correlated with their inhibitory effects on polyQ aggregation. We therefore conclude that SPR is a useful technique for screening for specific polyQ aggregation inhibitors as promising therapeutic candidates for the currently untreatable polyQ diseases.
authors.affiliation: Department of Molecular Biology and Cell Informatics, Graduate School of Life and Environment Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nagai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujikake
authors.forename: H
authors.initials: H
authors.lastname: Akiko Popiel
authors.forename: Tohru
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.forename: Takashi
authors.initials: T
authors.lastname: Inui
mesh_terms: D000595:Amino Acid Sequence; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D020349:Surface Plasmon Resonance
chemical_list: D009842:Oligopeptides; D010455:Peptides; C407346:polyglutamine-binding protein 1; C097188:polyglutamine