Identification of E2F-1/Cyclin A antagonists

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2449-52. doi: 10.1016/s0960-894x(01)00486-3.

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.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Biochemistry / methods
  • Cell Cycle Proteins*
  • Combinatorial Chemistry Techniques
  • Conserved Sequence
  • Cyclin A / antagonists & inhibitors*
  • DNA-Binding Proteins*
  • Drug Design
  • Drug Evaluation, Preclinical
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Enzyme-Linked Immunosorbent Assay
  • Inhibitory Concentration 50
  • Peptide Library
  • Peptides / chemistry*
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Structure-Activity Relationship
  • Transcription Factors / antagonists & inhibitors*

Substances

  • Cell Cycle Proteins
  • Cyclin A
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Peptide Library
  • Peptides
  • Transcription Factors