Synthesis, pharmacological evaluation, and molecular modeling studies of novel peptidic CAAX analogues as farnesyl-protein-transferase inhibitors

V Santagada, G Caliendo, B Severino…

Index: Santagada, Vincenzo; Caliendo, Giuseppe; Severino, Beatrice; Lavecchia, Antonio; Perissutti, Elisa; Fiorino, Ferdinando; Zampella, Angela; Sepe, Valentina; Califano, Daniela; Santelli, Giovanni; Novellino, Ettore Journal of Medicinal Chemistry, 2006 , vol. 49, # 6 p. 1882 - 1890

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Citation Number: 9

Abstract

Fifteen analogues of the C-terminal CA1A2X motif were synthesized and evaluated for their inhibition potency against farnesyltransferase (FTase). Replacement of the A2 residue by phenylalanine or tyrosine-derived analogues, in which a different number of methyl groups were introduced on the aromatic ring, resulted in compounds less active than the reference compound CVFM against FTase except for compounds I and VI (IC50= 1 μM and 2.5 μM, ...