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Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation
Christine M Wright1, Raj J Chovatiya, Nora E Jameson
1Department of Biological Sciences, University of Pittsburgh, 274 Crawford Hall, Pittsburgh, PA 15260, USA.
Abstract:
The Hsp70 molecular chaperones are ATPases that play critical roles in the pathogenesis of many human diseases, including breast cancer. Hsp70 ATP hydrolysis is relatively weak but is stimulated by J domain-containing proteins. We identified pyrimidinone-peptoid hybrid molecules that inhibit cell proliferation with greater potency than previously described Hsp70 modulators. In many cases, anti-proliferative activity correlated with inhibition of J domain stimulation of Hsp70.
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