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Journal of Biomolecular Screening
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Use of a Real-Time Fluorescence Monitoring System for High-Throughput Screening for Prolyl Isomerase Inhibitors

Tadashi Mori

Molecular Enzymology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan, Lead Generation Research Department, Medicinal Chemistry Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan

Seima Itami

Lead Generation Research Department, Medicinal Chemistry Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan

Tomotaka Yanagi

Lead Generation Research Department, Medicinal Chemistry Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan

Yota Tatara

Molecular Enzymology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan

Mari Takamiya

Lead Generation Research Department, Medicinal Chemistry Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan

Takafumi Uchida

Molecular Enzymology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan, uchidat{at}biochem.tohoku.ac.jp

Cyclophilin is a ubiquitous peptidyl prolyl cis/trans isomerase that plays critical roles in many biological processes. A number of cyclophilin inhibitors have been designed based on the structure of the immunosuppressant cyclosporin A. To discover inhibitors that have other structures, the authors established the high-throughput screening (HTS) method using FDSS6000 real-time fluorescence detector. The inhibitors identified with this HTS showed significant correlation with direct interaction as measured by surface plasmon resonance. This high-throughput assay system is a powerful tool for the discovery of peptidylprolyl isomerase inhibitors. (Journal of Biomolecular Screening 2009:419-424)

Key Words: peptidyl prolyl cis/trans isomerase • high-throughput screening • protease-coupled assay • cyclophilin • cyclosporin A

Journal of Biomolecular Screening, Vol. 14, No. 4, 419-424 (2009)
DOI: 10.1177/1087057109333979
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