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

doi:10.1016/j.bmc.2007.12.014

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 journal › Article › peer-review

92 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 language	English (US)
Pages (from-to)	3291-3301
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	6
DOIs	https://doi.org/10.1016/j.bmc.2007.12.014
State	Published - Mar 15 2008
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2007.12.014

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Wright, C. M., Chovatiya, R. J., Jameson, N. E., Turner, D. M., Zhu, G., Werner, S., Huryn, D. M., Pipas, J. M., Day, B. W., Wipf, P., & Brodsky, J. L. (2008). Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation. Bioorganic and Medicinal Chemistry, 16(6), 3291-3301. https://doi.org/10.1016/j.bmc.2007.12.014

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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.",

keywords = "ATP, ATPase, Apoptosis, Biginelli, Chaperone, Dihydropyrimidinone, Hsp40, Hsp70, J domain, SK-BR-3, SV40, T antigen, Tetrahydropyrimidinone, Ugi",

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

year = "2008",

month = mar,

day = "15",

doi = "10.1016/j.bmc.2007.12.014",

language = "English (US)",

volume = "16",

pages = "3291--3301",

journal = "Bioorganic and Medicinal Chemistry",

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number = "6",

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TY - JOUR

T1 - Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation

AU - Wright, Christine M.

AU - Chovatiya, Raj J.

AU - Jameson, Nora E.

AU - Turner, David M.

AU - Zhu, Guangyu

AU - Werner, Stefan

AU - Huryn, Donna M.

AU - Pipas, James M.

AU - Day, Billy W.

AU - Wipf, Peter

AU - Brodsky, Jeffrey L.

PY - 2008/3/15

Y1 - 2008/3/15

N2 - 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.

AB - 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.

KW - ATP

KW - ATPase

KW - Apoptosis

KW - Biginelli

KW - Chaperone

KW - Dihydropyrimidinone

KW - Hsp40

KW - Hsp70

KW - J domain

KW - SK-BR-3

KW - SV40

KW - T antigen

KW - Tetrahydropyrimidinone

KW - Ugi

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U2 - 10.1016/j.bmc.2007.12.014

DO - 10.1016/j.bmc.2007.12.014

M3 - Article

C2 - 18164205

AN - SCOPUS:40949083461

SN - 0968-0896

VL - 16

SP - 3291

EP - 3301

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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