Total synthesis and structure-activity relationship studies of a series of selective G protein inhibitors.

ABSTRACT: G proteins are key mediators of G protein-coupled receptor signalling, which facilitates a plethora of important physiological processes. The cyclic depsipeptides YM-254890 and FR900359 are the only known specific inhibitors of the G_q subfamily of G proteins; however, no synthetic route has been reported previously for these complex natural products and they are not easily isolated from natural sources. Here we report the first total synthesis of YM-254890 and FR900359, as well as of two known analogues, YM-385780 and YM-385781. The versatility of the synthetic approach also enabled the design and synthesis of ten analogues, which provided the first structure-activity relationship study for this class of compounds. Pharmacological characterization of all the compounds at G_q

SUBMITTER: Xiong XF 

PROVIDER: S-EPMC5559716 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature