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

C E O'Connell; C A Rowell; K Ackermann; A M Garcia; M D Lewis; J J Kowalczyk

doi:10.1248/cpb.48.740

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.

Authors

C E O'Connell¹, C A Rowell, K Ackermann, A M Garcia, M D Lewis, J J Kowalczyk

Affiliation

¹ Eisai Research Institute, Andover, MA 01810, USA.

PMID: 10823715
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