A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos
Artikel i vetenskaplig tidskrift, 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.

Författare

David Bliman

Göteborgs universitet

Jesper Nilsson

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Petronella Kettunen

Göteborgs universitet

Joakim Andreasson

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Morten Grötli

Göteborgs universitet

Scientific Reports

2045-2322 (ISSN)

Vol. 5 artikel nr 13109- 13109

Ämneskategorier

Biologiska vetenskaper

Kemi

DOI

10.1038/srep13109

PubMed

26300345