Document Report Card

ID: ALA1128452

Journal: J Med Chem

Title: Pseudodipeptide inhibitors of protein farnesyltransferase.

Authors: deSolms SJ, Deana AA, Giuliani EA, Graham SL, Kohl NE, Mosser SD, Oliff AI, Pompliano DL, Rands E, Scholz TH.

Abstract: A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previously reported, these inhibitors do not have a C-terminal carboxyl moiety, yet they inhibit farnesylation in vitro at < 100 nM. Despite the absence of the X residue in the CAAX motif, which normally directs prenylation specificity, these pseudodipeptides are greater than 100-fold selective for PFTase over type 1 protein geranylgeranyltransferase.

CiteXplore: 7562930

DOI: 10.1021/jm00020a010