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

Bioorg Med Chem Lett. 2014 Feb 1;24(3):786-9. doi: 10.1016/j.bmcl.2013.12.100. Epub 2014 Jan 2.

Authors

Steven M Johnson¹, Orzala Sharif², Puiying Annie Mak², Hsiao-Ting Wang², Ingo H Engels², Achim Brinker², Peter G Schultz³, Arthur L Horwich⁴, Eli Chapman⁵

Affiliations

¹ Indiana University, School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, USA.
² The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121, USA.
³ The Scripps Research Institute, Department of Chemistry, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
⁴ HHMI, Department of Genetics, Yale School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Ave., New Haven, CT 06510, USA. Electronic address: [email protected].
⁵ The University of Arizona, College of Pharmacy, Department of Pharmacology and Toxicology, 1703 E. Mabel St., PO Box 210207, Tucson, AZ 85721-0207, USA. Electronic address: [email protected].

PMID: 24418775
DOI: 10.1016/j.bmcl.2013.12.100

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chaperonin 10 / antagonists & inhibitors*
Chaperonin 60 / antagonists & inhibitors*
Dose-Response Relationship, Drug
Inhibitory Concentration 50
Models, Biological
Protein Folding / drug effects
Small Molecule Libraries / pharmacology*

Substances

Chaperonin 10
Chaperonin 60
Small Molecule Libraries