CH Activation Generates Period-Shortening Molecules That Target Cryptochrome in the Mammalian Circadian Clock

The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting-edge CH activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on K...

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Bibliographic Details
Published in:Angewandte Chemie 2015-06, Vol.127 (24), p.7299
Main Authors: Oshima, Tsuyoshi, Yamanaka, Iori, Kumar, Anupriya, Yamaguchi, Junichiro, Nishiwaki-Ohkawa, Taeko, Muto, Kei, Kawamura, Rika, Hirota, Tsuyoshi, Yagita, Kazuhiro, Irle, Stephan, Kay, Steve A, Yoshimura, Takashi, Itami, Kenichiro
Format: Article
Language:ger
Subjects:
Biological clocks
Chemistry
Circadian rhythm
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Summary:The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting-edge CH activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm-changing activity along with the components that trigger opposite modes of action. The first period-shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201502942