Brief Communication abstract
Nature Chemical Biology 4, 197 - 199 (2008)
Published online: 27 January 2008 | doi:10.1038/nchembio.65
Small-molecule aggregates inhibit amyloid polymerization
Brian Y Feng1, Brandon H Toyama2, Holger Wille3,4, David W Colby3, Sean R Collins2, Barnaby C H May3, Stanley B Prusiner3,4,5, Jonathan Weissman2 & Brian K Shoichet1
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 
-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.
- 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.
- Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California San Francisco and California Institute for Quantitative Biomedical Research, 1700 4th Street, San Francisco, California 94158, USA.
- Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California 94143-0518, USA.
- Department of Neurology, University of California San Francisco, San Francisco, California 94143-0518, USA.
- Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94143-0518, USA.
Correspondence to: Brian K Shoichet1 e-mail: shoichet@cgl.ucsf.edu
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