Cell-permeable high-affinity tracers for G_q proteins provide structural insights, reveal distinct binding kinetics and identify small molecule inhibitors.

ABSTRACT:

Background and purpose

G proteins are intracellular switches that transduce and amplify extracellular signals from GPCRs. The G_q protein subtypes, which are coupled to PLC activation, can act as oncogenes, and their expression was reported to be up-regulated in cancer and inflammatory diseases. G_q inhibition may be an efficient therapeutic strategy constituting a new level of intervention. However, diagnostic tools and therapeutic drugs for G_q proteins are lacking.

Experimental approach

We have now developed G_q -specific, cell-permeable ³ H-labelled high-affinity probes based on the macrocyclic depsipeptides FR900359 (FR) and YM-254890 (YM). The tracers served to specifically label and quantify G_q proteins in

SUBMITTER: Kuschak M 

PROVIDER: S-EPMC7070167 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature