Synthesis and evaluation of some hydroxyproline-derived peptidomimetics as isoprenyltransferase inhibitors

Chem Pharm Bull (Tokyo). 2000 May;48(5):740-2. doi: 10.1248/cpb.48.740.

Abstract

CA1A2X peptidomimetics containing a modified proline at position A2 were prepared and evaluated for their ability to inhibit farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) in enzymatic and cell-based assays. These compounds inhibited farnesylation of H-ras in vitro in the high nanomolar to low micromolar IC50 range.

MeSH terms

  • 3T3 Cells
  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Chemical Phenomena
  • Chemistry, Physical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Farnesyltranstransferase
  • Genes, ras / drug effects
  • Hydroxyproline / chemistry*
  • Mice
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis*
  • Proline / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Proline
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Farnesyltranstransferase
  • Hydroxyproline