This work was supported by the NIH AG028300 (P.W.) and by a grant from The Scripps Research Institute. The authors would like to thank R. P. Troseth (TSRI) for synthesis of 1 and Dr. P. R. Antrobus (OU) for high-resolution ES-MS of the synthetic peptides.
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Communication
Cholesterol Secosterol Adduction Inhibits the Misfolding of a Mutant Prion Protein Fragment that Induces Neurodegeneration†
Article first published online: 6 NOV 2009
DOI: 10.1002/anie.200904524
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Scheinost, Johanna C., Witter, Daniel P., Boldt, Grant E., Offer, J. and Wentworth, P. (2009), Cholesterol Secosterol Adduction Inhibits the Misfolding of a Mutant Prion Protein Fragment that Induces Neurodegeneration. Angew. Chem. Int. Ed., 48: 9469–9472. doi: 10.1002/anie.200904524
- †
Publication History
- Issue published online: 30 NOV 2009
- Article first published online: 6 NOV 2009
- Manuscript Received: 13 AUG 2009
Funded by
- NIH. Grant Number: AG028300
- The Scripps Research Institute
Keywords:
- atheronal;
- cholesterol;
- prion proteins;
- protein misfolding
Aldehyde is critical: Atheronal-B, a cholesterol secosterol aldehyde (see structure), completely inhibits the misfolding of a prion protein fragment from its α to β form through a mechanism that involves adduction to the protein. This result offers a fresh view of lipid aldehyde-induced protein misfolding and provides a promising molecular scaffold on which to develop potential prion disease therapeutics.