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

نویسندگان

  • Robert C Vasko
  • Rodrigo A Rodriguez
  • Christian N Cunningham
  • Veronica C Ardi
  • David A Agard
  • Shelli R McAlpine
چکیده

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.

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عنوان ژورنال:
  • ACS medicinal chemistry letters

دوره 1 1  شماره 

صفحات  -

تاریخ انتشار 2010