Identification of E2F-1/Cyclin A antagonists
S K Sharma1, T M Ramsey, Y N Chen
1Oncology Department, Novartis Institute for Biomedical Research, Summit, NJ 07901, USA. sushil.sharma@pharma.novartis.com
Abstract:
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 library of compounds mimicking the 'ZRXL' motif in order to identify E2F-1/Cyclin A antagonists. The synthesized compounds were evaluated in an E2F-1/Cyclin A binding assay and moderately active analogues were identified. In addition, the critical roles of Phe, Leu, Lys, and Arg residues of the identified motif were determined.
Related Concept Videos
Positive Regulator Molecules
Negative Regulator Molecules
Positive Regulator Molecules
Inhibition of Cdk Activity
Mitogens and the Cell Cycle
Inhibition of CDK Activity


