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CH Activation Generates Period‐Shortening Molecules That Target Cryptochrome in the Mammalian Circadian Clock
Author(s) -
Oshima Tsuyoshi,
Yamanaka Iori,
Kumar Anupriya,
Yamaguchi Junichiro,
NishiwakiOhkawa Taeko,
Muto Kei,
Kawamura Rika,
Hirota Tsuyoshi,
Yagita Kazuhiro,
Irle Stephan,
Kay Steve A.,
Yoshimura Takashi,
Itami Kenichiro
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201502942
Subject(s) - cryptochrome , circadian clock , circadian rhythm , period (music) , microbiology and biotechnology , biological clock , period length , biology , neuroscience , physics , discrete mathematics , acoustics , mathematics
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.