A microgonotropen pentaaza pentabutylamine and its interactions with DNA

Article abstract of DOI:10.1016/0968-0896(96)00070-3

The central pyrrole of a site-selective DNA minor groove binding tripyrrole peptide (1) has been attached to N-protected pentaazapentacosanoic acid (17) via a (CH₂)₃ NHCO (CH₂)₃ linker to provide 19, subsequent deprotection provided the pentaaza microgonotropen 4. The polyamine moiety of 4 reaches out of the minor groove and binds to the phosphate backbone of DNA. We find when employing Hoechst 33258 (Ht) as a fluorescent titrant to follow binding of 4 to the hexadecameric duplex d(GGCGCAAATTTGGCGG)/(CCGCCAAATTTGCGCC) and by ¹H NMR titration of d(CGCAAATTTGCG)₂ with 4 that the latter forms both 1:1 and 2:1 dsDNA complexes. Certain aspects of the structure of 4:d(CGCAAATTTGCG)₂ complex derived via ¹H NMR are discussed. The electrophoretic mobilities of φX-174 DNA digested with HaeIII endonuclease restriction fragments complexed to 4 shows that the latter brings about a greater conformational change in the DNA fragments than observed previously with other microgonotropens.