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Identification of E2F-1/Cyclin A antagonists.

Sharma, S K; Ramsey, T M; Chen, Y N; Chen, W; Martin, M S; Clune, K; Sabio, M; Bair, K W.

Bioorg Med Chem Lett ; 11(18): 2449-52, 2001 Sep 17.

Article in English | MEDLINE | ID: mdl-11549444

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.

Subject(s)

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

ABSTRACT

Subject(s)

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