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

• and, as we show, represents a unique and useful tool to probe tumor Hsp90 biology in live cells by affinity capture, flow cytometry and confocal microscopy. To our knowledge, 2g is the only reported biotinylated Hsp90 probe to have such combined characteristics. Keywords: affinity capture; biotin

• ; 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