Nonnucleosidic Base Surrogates: The Effect of 1,2‐Disubstituted Phenanthrenes on DNA Duplex Stability

Phenanthrene‐1,2‐dimethanol was incorporated into oligodeoxynucleotides via formation of phosphodiester bonds (cf. Scheme 1). If placed at internal positions in a DNA duplex, a strong reduction of duplex stability is observed (Table 1). Terminal attachment of stretches of phenanthrene residues, however, leads to a substantial increase in stability. The stabilization is attributed to a cooperative interaction of the phenanthrene residues of the two strands rather than to dangling end effects. Chimeric oligomers containing a stretch of six phenanthrene residues show two separate transitions (Table 2): one arising from the denaturation of the DNA stem (observable by a hyperchromic effect at 260 nm) and a second one from the denaturation of the phenanthrene part (observable by temperature‐dependant gel mobility assays). Based on these findings, a model of the chimeric hybrids is proposed, in which the phenanthrene residues stack in a zipper‐like manner on top of the DNA base pairs without disrupting the B‐form of the DNA stem (see Fig. 7).