Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation.
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.
Wright
Christine M
CM
Department of Biological Sciences, University of Pittsburgh, 274 Crawford Hall, Pittsburgh, PA 15260, USA.
Chovatiya
Raj J
RJ
Jameson
Nora E
NE
Turner
David M
DM
Zhu
Guangyu
G
Werner
Stefan
S
Huryn
Donna M
DM
Pipas
James M
JM
Day
Billy W
BW
Wipf
Peter
P
Brodsky
Jeffrey L
JL
D000251:Adenosine Triphosphatases / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D018832:Molecular Chaperones / Q000187:drug effects*; D034444:Peptoids / Q000737:chemistry / Q000494:pharmacology*; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology*
D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D034444:Peptoids; D011744:Pyrimidinones; D000251:Adenosine Triphosphatases