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 μM). 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.

Graphical abstractTylophorine B has favorable molecular interaction with bulged DNA, the oligo-deoxynucleotide, which has a tentative structure of a hairpin with a one base bulge, shows the tightest binding by tylophorine B with a dissociation constant of 18 nM.Figure optionsDownload full-size imageDownload as PowerPoint slide