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.