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

Article abstract of DOI:10.1016/S0968-0896(97)00011-4

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 K(L1)K(L2) 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.