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