Mechanistic Studies of Sansalvamide A-Amide: An Allosteric Modulator of Hsp90

Herein, we show that sansalvamide A-amide (San A-amide), a structurally unique molecule, influences a subset of cancer-related pathways involving heat shock protein 90 (Hsp90). We show that San A-amide specifically binds to the N-middle domain of Hsp90 and allosterically disrupts the binding of prot...

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Published in:ACS medicinal chemistry letters 2010-04, Vol.1 (1), p.4-8
Main Authors: Vasko, Robert C, Rodriguez, Rodrigo A, Cunningham, Christian N, Ardi, Veronica C, Agard, David A, McAlpine, Shelli R
Format: Article
Language:English
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Letter
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Summary:Herein, we show that sansalvamide A-amide (San A-amide), a structurally unique molecule, influences a subset of cancer-related pathways involving heat shock protein 90 (Hsp90). We show that San A-amide specifically binds to the N-middle domain of Hsp90 and allosterically disrupts the binding of proteins thought to interact with the Hsp90 C-terminal domain, while having no effect on an N-terminal domain client protein. This unique mechanism suggests that San A-amide is a potential tool for studying C-terminal binding proteins of Hsp90 as well as a promising lead in the development of new cancer therapeutics.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml900003t