Synthesis and Evaluation of Some Hydroxyproline-Derived Peptidomimetics as Isoprenyltransferase Inhibitors

Celeste E. O'CONNELL; Ceryl A. ROWELL; Karen ACKERMANN; Ana Maria GARCIA; Michael D. LEWIS; James J. KOWALCZYK

doi:10.1248/cpb.48.740

Celeste E. O'CONNELL, Ceryl A. ROWELL, Karen ACKERMANN, Ana Maria GARCIA, Michael D. LEWIS, James J. KOWALCZYK

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Keywords: farnesyltransferase inhibitor, CAAX, peptidomimetic, hydroxyproline, H-ras

JOURNAL FREE ACCESS

2000 Volume 48 Issue 5 Pages 740-742

DOI https://doi.org/10.1248/cpb.48.740

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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 cellbased assays. These compounds inhibited farnesylation of H-ras in vitro in the high nanomolar to low micromolar IC₅₀ range.

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