A small molecule that preferentially binds the closed conformation of Hsp90.
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.
Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182, USA.
Leslie D
LD
Alexander
James R
JR
Partridge
David A
DA
Agard
Shelli R
SR
McAlpine
D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D047630:Depsipeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D019793:Fluorescein / Q000737:chemistry; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation
D047630:Depsipeptides; D018841:HSP90 Heat-Shock Proteins; C119376:sansalvamide A; D000255:Adenosine Triphosphate; D019793:Fluorescein