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Bioorg Med Chem. 2012 Jun 1;20(11):3609-14. doi: 10.1016/j.bmc.2012.03.067. Epub 2012 Apr 11.

Novel inhibitors of heat shock protein Hsp70-mediated luciferase refolding that bind to DnaJ.

Author information

1
ALS Biopharma, LLC, Pennsylvania Biotechnology Center, 3805 Old Easton Rd, Doylestown, PA 18902, USA. jcassel@alsbiopharma.com

Abstract

Inhibitors of both heat shock proteins Hsp90 and Hsp70 have been identified in assays measuring luciferase refolding containing rabbit reticulocyte lysate or purified chaperone components. Here, we report the discovery of a series of phenoxy-N-arylacetamides that disrupt Hsp70-mediated luciferase refolding by binding to DnaJ, the bacterial homolog of human Hsp40. Inhibitor characterization experiments demonstrated negative cooperativity with respect to DnaJ and luciferase concentration, but varying the concentration of ATP had no effect on potency. Thermal shift analysis suggested a direct interaction with DnaJ, but not with Hsp70. These compounds may be useful tools for studying DnaJ/Hsp40 in various cellular processes.

PMID:
22546203
DOI:
10.1016/j.bmc.2012.03.067
[Indexed for MEDLINE]

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