Identification of E2F-1/Cyclin A antagonists

A simple method for the synthesis of a rationally designed (S,S ')-[Pro-Leu ]-spirolactam scaffold is described. This was expanded to a small biased li brary of compounds mimicking the 'ZRXL' motif in order to identify E2F-1/Cy clin A antagonists. The synthesized Compounds were evaluated in an E2F-1/Cy clin A binding assay and moderately active analogues were identified, In ad dition, the critical roles of Phe, Leu, Lys, and Arg residues of the identi fied motif were determined. (C) 2001 Elsevier Science Ltd. All rights reser ved.