Synthesis and evaluation of some hydroxyproline-derived peptidomimetics as isoprenyltransferase inhibitors.
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.
O'Connell
C E
CE
Eisai Research Institute, Andover, MA 01810, USA.
Rowell
C A
CA
Ackermann
K
K
Garcia
A M
AM
Lewis
M D
MD
Kowalczyk
J J
JJ
D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D011905:Genes, ras / Q000187:drug effects; D006909:Hydroxyproline / Q000737:chemistry*; D051379:Mice; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011392:Proline; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; D006909:Hydroxyproline