A small molecule that preferentially binds the closed conformation of Hsp90

Bioorg Med Chem Lett. 2011 Dec 1;21(23):7068-71. doi: 10.1016/j.bmcl.2011.09.096. Epub 2011 Sep 29.

Abstract

Described is the synthesis of three different fluorescein-tagged derivatives of a macrocycle, and their binding affinity to heat shock protein 90 (Hsp90). Using fluorescence polarization anisotropy, we report the binding affinity of these fluorescein-labeled compounds to Hsp90 in its open state and ATP-dependent closed state. We show that the compounds demonstrate a conformation-dependent preference for binding to the closed state.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • Depsipeptides / chemistry*
  • Depsipeptides / metabolism
  • Depsipeptides / pharmacology
  • Fluorescein / chemistry
  • HSP90 Heat-Shock Proteins / chemistry*
  • HSP90 Heat-Shock Proteins / metabolism
  • Molecular Structure
  • Protein Binding / drug effects
  • Protein Conformation

Substances

  • Depsipeptides
  • HSP90 Heat-Shock Proteins
  • sansalvamide A
  • Adenosine Triphosphate
  • Fluorescein