Synthesis and In Vitro Evaluation of the Ras Farnesyltransferase Inhibitor Pepticinnamin E.

A modularly built bisubstrate inhibitor, the natural product pepticinnamin E (shown on the right) was sythesized for the first time. In the case of in vitro assays it inhibits the enzyme farnesyltransferase with respect to both the peptide substrate and farnesylpyrophosphate (KI = 30 and 8 µM, respectively). The inhibitory activity is decisively influenced by the central tripeptide unit and the absolute configuration of the non-proteinogenic amino acid incorporated therein.