A microgonotropen branched decaaza decabutylamine and its DNA and DNA/transcription factor interactions Original Research Article

The central pyrrole of a site-selective DNA minor groove binding tripyrrole peptide 1 has been attached to a branched decaaza decabutylamine via a -(CH2)3-NHCO-(CH2)3- linker to provide the decaaza-microgonotropen (8). The decaaza decabutylamine moiety of 8 was designed to have a much greater affinity to the phosphodiester linkages of the backbone of DNA. Employing Hoechst 33258 (Ht) as a fluorescent titrant, the equilibrium constants for the binding of 8 to the hexadecameric duplex d(GGCGCA3T3GGCGG)/d(CCGCCA3T3GCGCC) and to calf thymus DNA were determined. The log of the product of equilibrium constants (log K1.1K1.2) for 1:1 and 1:2 complexes formation at A3T3 is 17 (35°C). Results of studies of the inhibition of the binding of several proteins to target DNA are discussed. Binding of the E2F1 transcription factor to its DNA target is 50% inhibited at ∼2 nM concentration of 8.