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Angew Chem Int Ed Engl. 2014 Feb 17;53(8):2110-3. doi: 10.1002/anie.201307465. Epub 2014 Jan 22.

A photocleavable masked nuclear-receptor ligand enables temporal control of C. elegans development.

Author information

1
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, 1 Tower Road, Ithaca, New York 14853 (USA) http://bti.cornell.edu/schroeder.

Erratum in

  • Angew Chem Int Ed Engl. 2014 May 12;53(20):4994.

Abstract

The development and lifespan of C. elegans are controlled by the nuclear hormone receptor DAF-12, an important model for the vertebrate vitamin D and liver X receptors. As with its mammalian homologues, DAF-12 function is regulated by bile acid-like steroidal ligands; however, tools for investigating their biosynthesis and function in vivo are lacking. A flexible synthesis for DAF-12 ligands and masked ligand derivatives that enable precise temporal control of DAF-12 function was developed. For ligand masking, photocleavable amides of 5-methoxy-N-methyl-2-nitroaniline (MMNA) were introduced. MMNA-masked ligands are bioavailable and after incorporation into the worm, brief UV irradiation can be used to trigger the expression of DAF-12 target genes and initiate development from dauer larvae into adults. The in vivo release of DAF-12 ligands and other small-molecule signals by using photocleavable MMNA-masked ligands will enable functional studies with precise spatial and temporal resolution.

KEYWORDS:

amides; gene expression; photolysis; small-molecule signaling; steroid hormones

PMID:
24453122
PMCID:
PMC4016105
DOI:
10.1002/anie.201307465
[Indexed for MEDLINE]
Free PMC Article

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