A Small Molecule Modulates Circadian Rhythms through Phosphorylation of the Period Protein†
Dr. Jae Wook Lee
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
These authors contributed equally to this work.
Search for more papers by this authorDr. Tsuyoshi Hirota
Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
These authors contributed equally to this work.
Search for more papers by this authorDr. Eric C. Peters
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorDr. Michael Garcia
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorDr. Rodolfo Gonzalez
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Search for more papers by this authorDr. Charles Y. Cho
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorDr. Xu Wu
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorCorresponding Author
Prof. Peter G. Schultz
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Peter G. Schultz, Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Steve A. Kay, Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
Search for more papers by this authorCorresponding Author
Prof. Steve A. Kay
Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
Peter G. Schultz, Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Steve A. Kay, Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
Search for more papers by this authorDr. Jae Wook Lee
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
These authors contributed equally to this work.
Search for more papers by this authorDr. Tsuyoshi Hirota
Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
These authors contributed equally to this work.
Search for more papers by this authorDr. Eric C. Peters
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorDr. Michael Garcia
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorDr. Rodolfo Gonzalez
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Search for more papers by this authorDr. Charles Y. Cho
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorDr. Xu Wu
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121 (USA)
Search for more papers by this authorCorresponding Author
Prof. Peter G. Schultz
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Peter G. Schultz, Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Steve A. Kay, Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
Search for more papers by this authorCorresponding Author
Prof. Steve A. Kay
Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
Peter G. Schultz, Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Steve A. Kay, Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
Search for more papers by this authorWe thank Dr. Warren G. Lewis, Paul Anderson, Jason Matzen, Jeff Janes, and Dr. Achim Brinker for compound screening and Francis Peters for critical reading of the manuscript. This work was funded in part by grants from the NIH (R01 GM074868, R01 MH051573, and P50 GM085764 to S.A.K.) and the Skaggs Institute for Chemical Biology (to P.G.S).
Graphical Abstract
Zeitverschiebung: Ein zellbasiertes Hochdurchsatz-Screening lieferte ein Benzothiazolanalogon, LH846, das die Phasen des Tag-Nacht-Rhythmus verlängert. Affinitätschromatographie in Kombination mit massenspektrometrischer und genomischer Analyse identifizierte die Proteinkinase CKIδ als das biologische Ziel von LH846 (siehe Bild).
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