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

• promoting molecular characterization of biomolecules both in vitro and within their natural biological contexts. In one application, biotinylated probes may be subjected to streptavidin-containing beads to identify potential direct and indirect interactors of the small molecule through affinity capture

• oncogenic Hsp90 and its complexes from live cells by affinity capture, flow cytometry and microscopy. Of all probes, we found only 2g to be very effective at both permeating cancer cell membranes and binding to and isolating Hsp90 onco-protein complexes from live cells (Figure 2a and d; red boxes), and its