Controlling the Circadian Clock with High Temporal Resolution Through Photodosing

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Sep 12

PMID 31509406

Citations 24

Authors

Dusan Kolarski

Akiko Sugiyama

Ghislain Breton

Christin Rakers

Daisuke Ono

Albert Schulte

Florence Tama

Kenichiro Itami

Wiktor Szymanski

Tsuyoshi Hirota

Ben L Feringa

Affiliations

Soon will be listed here.

Abstract

Circadian clocks, biological timekeepers that are present in almost every cell of our body, are complex systems whose disruption is connected to various diseases. Controlling cellular clock function with high temporal resolution in an inducible manner would yield an innovative approach for the circadian rhythm regulation. In the present study, we present structure-guided incorporation of photoremovable protecting groups into a circadian clock modifier, longdaysin, which inhibits casein kinase I (CKI). Using photodeprotection by UV or visible light (400 nm) as the external stimulus, we have achieved quantitative and light-inducible control over the CKI activity accompanied by an accurate regulation of circadian period in cultured human cells and mouse tissues, as well as in living zebrafish. This research paves the way for the application of photodosing in achieving precise temporal control over the biological timing and opens the door for chronophotopharmacology to deeper understand the circadian clock system.

Citing Articles

Abraham Patchornik: The Contemporary Relevance of His Work for Chemistry and Biology.

Jacobson K, Ellis-Davies G JACS Au. 2025; 5(1):3-16.

PMID: 39886589 PMC: 11775701. DOI: 10.1021/jacsau.4c00779.

Synthesis and Application of Photocaged Isopropyl β-D-1-Thiogalactopyranoside for Light-Mediated Control of Bacterial Gene Expression.

Knapp F, Hogenkamp F, Paik S, Jaeger K, Pietruszka J, Drepper T Methods Mol Biol. 2024; 2840:133-148.

PMID: 39724349 DOI: 10.1007/978-1-0716-4047-0_10.

A High-Quality Photoswitchable Probe that Selectively and Potently Regulates the Transcription Factor RORγ.

Reynders M, Willems S, Marschner J, Wein T, Merk D, Thorn-Seshold O Angew Chem Int Ed Engl. 2024; 63(49):e202410139.

PMID: 39248642 PMC: 11586699. DOI: 10.1002/anie.202410139.

Dissecting the Interaction between Cryptochrome and Timeless Reveals Underpinnings of Light-Dependent Recognition.

Schneps C, Dunleavy R, Crane B Biochemistry. 2024; .

PMID: 38294880 PMC: 11289166. DOI: 10.1021/acs.biochem.3c00630.

Differential Regulation of Circadian Clock Genes by UV-B Radiation and 1,25-Dihydroxyvitamin D: A Pilot Study during Different Stages of Skin Photocarcinogenesis.

Lamnis L, Christofi C, Stark A, Palm H, Roemer K, Vogt T Nutrients. 2024; 16(2).

PMID: 38257148 PMC: 10820546. DOI: 10.3390/nu16020254.

References

Eide E, Woolf M, Kang H, Woolf P, Hurst W, Camacho F . Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation. Mol Cell Biol. 2005; 25(7):2795-807. PMC: 1061645. DOI: 10.1128/MCB.25.7.2795-2807.2005. View

Kolarski D, Szymanski W, Feringa B . Two-Step, One-Pot Synthesis of Visible-Light-Responsive 6-Azopurines. Org Lett. 2017; 19(19):5090-5093. PMC: 5633830. DOI: 10.1021/acs.orglett.7b02361. View

Ferguson F, Gray N . Kinase inhibitors: the road ahead. Nat Rev Drug Discov. 2018; 17(5):353-377. DOI: 10.1038/nrd.2018.21. View

Bass J, Lazar M . Circadian time signatures of fitness and disease. Science. 2016; 354(6315):994-999. DOI: 10.1126/science.aah4965. View

Etchegaray J, Machida K, Noton E, Constance C, Dallmann R, Di Napoli M . Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol Cell Biol. 2009; 29(14):3853-66. PMC: 2704743. DOI: 10.1128/MCB.00338-09. View

Solt L, Wang Y, Banerjee S, Hughes T, Kojetin D, Lundasen T . Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012; 485(7396):62-8. PMC: 3343186. DOI: 10.1038/nature11030. View

Velema W, Szymanski W, Feringa B . Photopharmacology: beyond proof of principle. J Am Chem Soc. 2014; 136(6):2178-91. DOI: 10.1021/ja413063e. View

Xu Y, Padiath Q, Shapiro R, Jones C, Wu S, Saigoh N . Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature. 2005; 434(7033):640-4. DOI: 10.1038/nature03453. View

Hirota T, Kay S . Identification of small-molecule modulators of the circadian clock. Methods Enzymol. 2015; 551:267-82. DOI: 10.1016/bs.mie.2014.10.015. View

10.

Levitzki A . Protein kinase inhibitors as a therapeutic modality. Acc Chem Res. 2003; 36(6):462-9. DOI: 10.1021/ar0201207. View

11.

Oshima T, Niwa Y, Kuwata K, Srivastava A, Hyoda T, Tsuchiya Y . Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth. Sci Adv. 2019; 5(1):eaau9060. PMC: 6357737. DOI: 10.1126/sciadv.aau9060. View

12.

Hirota T, Lewis W, Liu A, Lee J, Schultz P, Kay S . A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3beta. Proc Natl Acad Sci U S A. 2008; 105(52):20746-51. PMC: 2606900. DOI: 10.1073/pnas.0811410106. View

13.

Velema W, van der Berg J, Szymanski W, Driessen A, Feringa B . Orthogonal control of antibacterial activity with light. ACS Chem Biol. 2014; 9(9):1969-74. DOI: 10.1021/cb500313f. View

14.

Gorostiza P, Isacoff E . Optical switches for remote and noninvasive control of cell signaling. Science. 2008; 322(5900):395-9. PMC: 7592022. DOI: 10.1126/science.1166022. View

15.

Hirota T, Lee J, St John P, Sawa M, Iwaisako K, Noguchi T . Identification of small molecule activators of cryptochrome. Science. 2012; 337(6098):1094-7. PMC: 3589997. DOI: 10.1126/science.1223710. View

16.

Oshima T, Yamanaka I, Kumar A, Yamaguchi J, Nishiwaki-Ohkawa T, Muto K . C-H activation generates period-shortening molecules that target cryptochrome in the mammalian circadian clock. Angew Chem Int Ed Engl. 2015; 54(24):7193-7. DOI: 10.1002/anie.201502942. View

17.

Sitkowska K, Feringa B, Szymanski W . Green-Light-Sensitive BODIPY Photoprotecting Groups for Amines. J Org Chem. 2018; 83(4):1819-1827. PMC: 5822223. DOI: 10.1021/acs.joc.7b02729. View

18.

Shinohara Y, Koyama Y, Ukai-Tadenuma M, Hirokawa T, Kikuchi M, Yamada R . Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock. Mol Cell. 2017; 67(5):783-798.e20. DOI: 10.1016/j.molcel.2017.08.009. View

19.

Isojima Y, Nakajima M, Ukai H, Fujishima H, Yamada R, Masumoto K . CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock. Proc Natl Acad Sci U S A. 2009; 106(37):15744-9. PMC: 2736905. DOI: 10.1073/pnas.0908733106. View

20.

Toh K, Jones C, He Y, Eide E, Hinz W, Virshup D . An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science. 2001; 291(5506):1040-3. DOI: 10.1126/science.1057499. View