A biochemical screen for GroEL/GroES inhibitors

Steven M. Johnson; Orzala Sharif; Puiying Annie Mak; Hsiao Ting Wang; Ingo H. Engels; Achim Brinker; Peter G. Schultz; Arthur L. Horwich; Eli Chapman

doi:10.1016/j.bmcl.2013.12.100

A biochemical screen for GroEL/GroES inhibitors

Steven M. Johnson
, Orzala Sharif
, Puiying Annie Mak
, Hsiao Ting Wang
, Ingo H. Engels
, Achim Brinker
, Peter G. Schultz
, Arthur L. Horwich
, Eli Chapman

Pharmacology and Toxicology

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

High-throughput screening of 700,000 small molecules has identified 235 inhibitors of the GroEL/GroES-mediated refolding cycle. Dose-response analysis of a subset of these hits revealed that 21 compounds are potent inhibitors of GroEL/GroES-mediated refolding (IC₅₀ <10 μM). The screening results presented herein represent the first steps in a broader aim of developing molecular probes to study chaperonin biochemistry and physiology.

Original language	English (US)
Pages (from-to)	786-789
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2013.12.100
State	Published - Feb 1 2014

Keywords

Chaperonin
GroEL
GroES
High-throughput screening
Small molecule inhibitors

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2013.12.100

Cite this

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title = "A biochemical screen for GroEL/GroES inhibitors",

abstract = "High-throughput screening of 700,000 small molecules has identified 235 inhibitors of the GroEL/GroES-mediated refolding cycle. Dose-response analysis of a subset of these hits revealed that 21 compounds are potent inhibitors of GroEL/GroES-mediated refolding (IC50 <10 μM). The screening results presented herein represent the first steps in a broader aim of developing molecular probes to study chaperonin biochemistry and physiology.",

keywords = "Chaperonin, GroEL, GroES, High-throughput screening, Small molecule inhibitors",

author = "Johnson, \{Steven M.\} and Orzala Sharif and Mak, \{Puiying Annie\} and Wang, \{Hsiao Ting\} and Engels, \{Ingo H.\} and Achim Brinker and Schultz, \{Peter G.\} and Horwich, \{Arthur L.\} and Eli Chapman",

note = "Funding Information: This research was supported by funding from the Genomics Institute of the Novartis Research Foundation (GNF) and The Scripps Research Institute. We are grateful for the assistance of George Farr, Wayne Fenton, and other members of the Horwich lab. The technical expertise of Michael Garcia, Jason Matzen, Richard Trager, Arnab Chatterjee, and other members of the Genomics Institute of the Novartis Research Foundation are also greatly appreciated. ",

year = "2014",

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day = "1",

doi = "10.1016/j.bmcl.2013.12.100",

language = "English (US)",

volume = "24",

pages = "786--789",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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TY - JOUR

T1 - A biochemical screen for GroEL/GroES inhibitors

AU - Johnson, Steven M.

AU - Sharif, Orzala

AU - Mak, Puiying Annie

AU - Wang, Hsiao Ting

AU - Engels, Ingo H.

AU - Brinker, Achim

AU - Schultz, Peter G.

AU - Horwich, Arthur L.

AU - Chapman, Eli

N1 - Funding Information: This research was supported by funding from the Genomics Institute of the Novartis Research Foundation (GNF) and The Scripps Research Institute. We are grateful for the assistance of George Farr, Wayne Fenton, and other members of the Horwich lab. The technical expertise of Michael Garcia, Jason Matzen, Richard Trager, Arnab Chatterjee, and other members of the Genomics Institute of the Novartis Research Foundation are also greatly appreciated.

PY - 2014/2/1

Y1 - 2014/2/1

N2 - High-throughput screening of 700,000 small molecules has identified 235 inhibitors of the GroEL/GroES-mediated refolding cycle. Dose-response analysis of a subset of these hits revealed that 21 compounds are potent inhibitors of GroEL/GroES-mediated refolding (IC50 <10 μM). The screening results presented herein represent the first steps in a broader aim of developing molecular probes to study chaperonin biochemistry and physiology.

AB - High-throughput screening of 700,000 small molecules has identified 235 inhibitors of the GroEL/GroES-mediated refolding cycle. Dose-response analysis of a subset of these hits revealed that 21 compounds are potent inhibitors of GroEL/GroES-mediated refolding (IC50 <10 μM). The screening results presented herein represent the first steps in a broader aim of developing molecular probes to study chaperonin biochemistry and physiology.

KW - Chaperonin

KW - GroEL

KW - GroES

KW - High-throughput screening

KW - Small molecule inhibitors

UR - https://www.scopus.com/pages/publications/84893684183

UR - https://www.scopus.com/pages/publications/84893684183#tab=citedBy

U2 - 10.1016/j.bmcl.2013.12.100

DO - 10.1016/j.bmcl.2013.12.100

M3 - Article

C2 - 24418775

AN - SCOPUS:84893684183

SN - 0960-894X

VL - 24

SP - 786

EP - 789

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 3

ER -

A biochemical screen for GroEL/GroES inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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