A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos
Journal article, 2015

Proto-oncogene tyrosine-protein kinase receptor RET is implicated in the development and maintenance of neurons of the central and peripheral nervous systems. Attaching activity-compromising photocleavable groups (caging) to inhibitors could allow for external spatiotemporally controlled inhibition using light, potentially providing novel information on how these kinase receptors are involved in cellular processes. Here, caged RET inhibitors were obtained from 3-substituted pyrazolopyrimidine-based compounds by attaching photolabile groups to the exocyclic amino function. The most promising compound displayed excellent inhibitory effect in cell-free, as well as live-cell assays upon decaging. Furthermore, inhibition could be efficiently activated with light in vivo in zebrafish embryos and was shown to effect motoneuron development.

Author

David Bliman

University of Gothenburg

Jesper Nilsson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Petronella Kettunen

University of Gothenburg

Joakim Andreasson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Morten Grötli

University of Gothenburg

Scientific Reports

2045-2322 (ISSN)

Vol. 5 artikel nr 13109- 13109

Photonic switching of molecular properties using photochromes

Swedish Research Council (VR), 2011-01-01 -- 2016-12-31.

Photochromic Systems for Solid State Molecular Electronic Devices and Light-Activated Cancer Drugs (PHOTOCHROMES)

European Commission (FP7), 2008-09-01 -- 2013-08-31.

Subject Categories

Biological Sciences

Chemical Sciences

DOI

10.1038/srep13109

PubMed

26300345

More information

Latest update

4/18/2018