April 15, 2015

Toward the Selective Inhibition of G Proteins: Total Synthesis of a Simplified YM-​254890 Analog

Rensing, Derek T.; Uppal, Sakshi; Blumer, Kendall J. and  Moeller, Kevin D.

Organic Letters, 2015, Ahead of Print

A simplified analog (WU-​07047) of the selective Gαq​/11 inhibitor YM-​254890 has been synthesized, and an initial probe of its activity conducted.  In the analog, the two peptide-​based linkers in the cyclic YM-​254890 have been replaced with hydrocarbon chains.  This enables a convergent approach to the synthesis of the analog.  Biochem. assays showed that while the simplified analog is not as potent as YM-​254890, it does still inhibit Gq.