Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• biology. Here, we present a systematic approach to identify biotinylated analogues of the Hsp90 inhibitor PU-H71 that are capable of permeating cell membranes so as to enable the investigation of Hsp90 complexes in live cells. The identified derivative 2g can isolate Hsp90 through affinity purification

• ; flow cytometry; fluorescence microscopy; PU-H71; tumor Hsp90; Introduction Heat shock protein 90 (Hsp90) is a molecular chaperone that functions to properly fold proteins to their active conformation through its ATPase activity [1]. These client proteins include many that are involved in malignant

• interest is the purine scaffold, including its representative PU-H71 (1a). This agent, currently in clinical investigation for cancer, binds to the N-terminal nucleotide binding pocket of Hsp90 [12]. We have shown that PU-H71 selects for tumor Hsp90 species, and therefore labeled derivatives of PU-H71 may