Selective interaction between tylophorine B and bulged DNA.

Tylophorine B exhibits pronounced cytotoxicity and antitumor activity. In order to survey the structure selectivity to DNA afforded by tylophorine B, we have synthesized a variety of duplex, bulge- and hairpin-containing oligodeoxyribonucleotides. Their binding to tylophorine B has been assayed by fluorescence spectroscopy and thermal melting experiments. The results indicate that oligonucleotides interact with tylophorine B at submicromolar concentration, and the affinity for DNA bulge is optimal (with Kd of 0.018 microM). In addition, the bulged hairpin oligonucleotides are stabilized by binding to tylophorine B. These findings may shed some light on tylophorine B's mode of action in biological systems and result in the rational design of sequence-specific DNA binding molecules.