title: Small-molecule aggregates inhibit amyloid polymerization.
abstract: Many amyloid inhibitors resemble molecules that form chemical aggregates, which are known to inhibit many proteins. Eight known chemical aggregators inhibited amyloid formation of the yeast and mouse prion proteins Sup35 and recMoPrP in a manner characteristic of colloidal inhibition. Similarly, three known anti-amyloid molecules inhibited beta-lactamase in a detergent-dependent manner, which suggests that they too form colloidal aggregates. The colloids localized to preformed fibers and prevented new fiber formation in electron micrographs. They also blocked infection of yeast cells with Sup35 prions, which suggests that colloidal inhibition may be relevant in more biological milieus.
authors.affiliation: Department of Pharmaceutical Chemistry and Graduate Group in Chemistry and Chemical Biology, University of California San Francisco, 1700 4th Street, San Francisco, California 94158-2330, USA.
authors.forename: Brian Y
authors.initials: BY
authors.lastname: Feng
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Toyama
authors.forename: Holger
authors.initials: H
authors.lastname: Wille
authors.forename: David W
authors.initials: DW
authors.lastname: Colby
authors.forename: Sean R
authors.initials: SR
authors.lastname: Collins
authors.forename: Barnaby C H
authors.initials: BC
authors.lastname: May
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weissman
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
mesh_terms: D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D007464:Clioquinol / Q000737:chemistry / Q000494:pharmacology*; D003224:Congo Red / Q000737:chemistry / Q000494:pharmacology*; D003902:Detergents / Q000737:chemistry; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D015394:Molecular Structure; D008970:Molecular Weight; D010316:Particle Size; D010454:Peptide Termination Factors; D010635:Phenolphthaleins / Q000737:chemistry / Q000494:pharmacology*; D010797:Phthalimides / Q000737:chemistry / Q000494:pharmacology*; D011328:Prions / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
chemical_list: C117146:4,5-bis(4-fluoroanilino)phthalimide; D000098:Acetophenones; D001578:Benzopyrans; D003902:Detergents; D044950:Flavanones; D010454:Peptide Termination Factors; D010635:Phenolphthaleins; D010797:Phthalimides; D011328:Prions; D011994:Recombinant Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D065093:beta-Lactamase Inhibitors; C531044:tetraiodophenolphthalein; D003224:Congo Red; C006680:baicalein; D007464:Clioquinol; C085746:rottlerin; D001618:beta-Lactamases