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Mechanistic studies of Sansalvamide A-amide: an allosteric modulator of Hsp90.

ABSTRACT: Herein we show that San A-amide, a structurally unique molecule, influences a subset of cancer-related pathways involving Hsp90. We show that San A-amide specifically binds to the N-middle domain of Hsp90 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.

SUBMITTER: Vasko RC

PROVIDER: S-EPMC2922868 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Mechanistic studies of Sansalvamide A-amide: an allosteric modulator of Hsp90.

Vasko Robert C RC Rodriguez Rodrigo A RA Cunningham Christian N CN Ardi Veronica C VC Agard David A DA McAlpine Shelli R SR

ACS medicinal chemistry letters 20100101 1

Herein we show that San A-amide, a structurally unique molecule, influences a subset of cancer-related pathways involving Hsp90. We show that San A-amide specifically binds to the N-middle domain of Hsp90 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 ...[more]

PMID: 20730035

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