Exploiting polarity and chirality to probe the Hsp90 C-terminus

  • Bioorg Med Chem. 2018 Jul 23;26(12):3096-3110. doi: 10.1016/j.bmc.2018.04.028.
Leah K Forsberg  1 ,  Rachel E Davis  1 ,  Virangika K Wimalasena  1 ,  Brian S J Blagg  2
Affiliations
  • 1. Department of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN 46556 USA.
  • 2. Department of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN 46556 USA. Electronic address: [email protected].
PMID: 29720349 DOI: 10.1016/j.bmc.2018.04.028
Abstract

Inhibition of the HSP90 C-terminus is an attractive therapeutic approach for the treatment of Cancer. Novobiocin, the first HSP90 C-terminal inhibitor identified, contains a synthetically complex noviose sugar that has limited the generation of structure-activity relationships for this region of the molecule. The work described herein utilizes various ring systems as noviose surrogates to explore the size and nature of the surrounding binding pocket.