Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation

Christine M. Wright, Raj J. Chovatiya, Nora E. Jameson, David M. Turner, Guangyu Zhu, Stefan Werner, Donna M. Huryn, James M. Pipas, Billy W. Day, Peter Wipf, Jeffrey L. Brodsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3291-3301
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number6
DOIs
StatePublished - Mar 15 2008
Externally publishedYes

Keywords

  • ATP
  • ATPase
  • Apoptosis
  • Biginelli
  • Chaperone
  • Dihydropyrimidinone
  • Hsp40
  • Hsp70
  • J domain
  • SK-BR-3
  • SV40
  • T antigen
  • Tetrahydropyrimidinone
  • Ugi

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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