Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors

Y Qian, JJ Marugan, RD Fossum, A Vogt…

Index: Qian, Yimin; Marugan, Juan Jose; Fossum, Renae D.; Vogt, Andreas; Sebti, Said M.; Hamilton, Andrew D. Bioorganic and Medicinal Chemistry, 1999 , vol. 7, # 12 p. 3011 - 3024

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Citation Number: 44

Abstract

Cysteine farnesylation at the carboxylate terminal tetrapeptide CAAX of Ras protein is catalyzed by farnesyltransferase. This lipid modification is necessary for regulatory function of both normal and oncogenic Ras. The high frequency of Ras mutation in human cancers has prompted an intensive study on finding ways of controlling oncogenic Ras function. Inhibition of farnesyltransferase is among the most sought after targets for cancer ...