Benzodiazepine peptidomimetic inhibitors of farnesyltransferase.

  title={Benzodiazepine peptidomimetic inhibitors of farnesyltransferase.},
  author={J. C. Marsters and Robert S. McDowell and Mark R. Ter Molen Evan M. Tager Sarah E. Reynolds and David Oare and Th. Somers and Michele S. Stanley and Thomas E Rawson and Martin E Struble and D. J. Burdick and Kin Shing Chan},
  journal={Bioorganic & medicinal chemistry},
  volume={2 9},
A structural survey of protein Zn2+ binding geometries was instigated based upon the functional requirement of Ras farnesyltransferase for Zn2+. The Cys-X-X-Cys motif found in Zn(2+)-binding proteins such as aspartate transcarbamylase was used as a template to devise a bidentate-coordination model for Cys-A1-A2-X peptide inhibitors. Accordingly, replacement of the central dipeptide with the hydrophobic scaffold 3-amino-1-carboxymethyl-2,3-dihydro-5- phenyl-1H-1,4-benzodiazepin-2-one (BZA… CONTINUE READING