title: Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation.
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.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, 274 Crawford Hall, Pittsburgh, PA 15260, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Wright
authors.forename: Raj J
authors.initials: RJ
authors.lastname: Chovatiya
authors.forename: Nora E
authors.initials: NE
authors.lastname: Jameson
authors.forename: David M
authors.initials: DM
authors.lastname: Turner
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
authors.forename: Stefan
authors.initials: S
authors.lastname: Werner
authors.forename: Donna M
authors.initials: DM
authors.lastname: Huryn
authors.forename: James M
authors.initials: JM
authors.lastname: Pipas
authors.forename: Billy W
authors.initials: BW
authors.lastname: Day
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Brodsky
mesh_terms: 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*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D034444:Peptoids; D011744:Pyrimidinones; D000251:Adenosine Triphosphatases