Synthesis and biological activity of ras farnesyl protein transferase inhibitors. Tetrapeptide analogs with amino methyl and carbon linkages

Bioorg Med Chem. 1994 Sep;2(9):939-47. doi: 10.1016/s0968-0896(00)82043-x.

Abstract

Replacement of the central amino methylene linkage of C[psi CH2NH]A[psi CH2NH]AX tetrapeptide inhibitors with carbon tethers led to compounds with potency in the nanomolar range. Some of the more potent olefinic compounds inhibit Ras processing in intact v-ras transformed NIH 3T3 cells with IC50 values in the 0.1 to 1 microM range, and inhibit selectively the anchorage-independent growth of H-ras transformed Rat1 cells at 10 microM.

MeSH terms

  • 3T3 Cells
  • Alkyl and Aryl Transferases*
  • Amino Acid Sequence
  • Animals
  • Cell Transformation, Viral
  • Genes, ras
  • Mice
  • Molecular Sequence Data
  • Molecular Structure
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Transferases / antagonists & inhibitors*

Substances

  • Oligopeptides
  • Transferases
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase