A combinatorial approach to new DNA minor groove binders.
A combinatorial approach towards new DNA minor groove binders capable of recognizing GC base pairs is reported. From a partly AT--biased library of 5832 different octapeptides of the type Py-Py-X1-X2-X3-Py-Py-gamma Abu synthesized following the one bead one compound methodology, two compounds containing the central peptide sequences Val-beta Ala-Tyr and Pip-beta Ala-Tyr were selected by a fluorescence--double stranded DNA probing assay using the sequence 5'-TTTGTTT-3' as the probe. The two hits were independently synthesized and binding to a recombinant pUC-19 EcoRl/Pvull DNA restriction fragment containing the sequence 5'-TTTGTTT-3' demonstrated. Binding constants to eight targets in the DNA fragment were estimated from quantitative DNAse I footprinting.
Behrens
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Department of Chemistry, University of Copenhagen, Denmark.
Nielsen
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PE
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites; D001671:Biochemistry / Q000379:methods; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D018983:DNA Footprinting; D015342:DNA Probes; D003850:Deoxyribonuclease I / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D015342:DNA Probes; D010455:Peptides; D004247:DNA; D003850:Deoxyribonuclease I