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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.

SUBMITTER: Feng BY

PROVIDER: S-EPMC2730835 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Small-molecule aggregates inhibit amyloid polymerization.

Feng Brian Y BY Toyama Brandon H BH Wille Holger H Colby David W DW Collins Sean R SR May Barnaby C H BC Prusiner Stanley B SB Weissman Jonathan J Shoichet Brian K BK

Nature chemical biology 20080127 3

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 prevent ...[more]

PMID: 18223646

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