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.
authors.affiliation: Indiana University, School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Johnson
authors.affiliation: The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121, USA.
authors.forename: Orzala
authors.initials: O
authors.lastname: Sharif
authors.affiliation: The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121, USA.
authors.forename: Puiying Annie
authors.initials: PA
authors.lastname: Mak
authors.affiliation: The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121, USA.
authors.forename: Hsiao-Ting
authors.initials: HT
authors.lastname: Wang
authors.affiliation: The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121, USA.
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Engels
authors.affiliation: The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121, USA.
authors.forename: Achim
authors.initials: A
authors.lastname: Brinker
authors.affiliation: The Scripps Research Institute, Department of Chemistry, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
authors.affiliation: HHMI, Department of Genetics, Yale School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Ave., New Haven, CT 06510, USA. Electronic address: arthur.horwich@yale.edu.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Horwich
authors.affiliation: 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: chapman@pharmacy.arizona.edu.
authors.forename: Eli
authors.initials: E
authors.lastname: Chapman
mesh_terms: D018835:Chaperonin 10 / Q000037:antagonists & inhibitors*; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D017510:Protein Folding / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; D054852:Small Molecule Libraries
keywords: Chaperonin; GroEL; GroES; High-throughput screening; Small molecule inhibitors