Sequence-specific and hydrolytic scission of DNA and RNA by lanthanide complex-oligoDNA hybrids.

Abstract

Totally synthetic and sequence-specific nucleases and ribonucleases, which hydrolyze DNAs and RNAs selectively at target sites, have been prepared. Lanthanide ions, which efficiently hydrolyze the phosphodiester linkages in nucleic acids, are attached to the 5'-end of synthetic DNA oligomers (sequence-recognizing sites) by use of an iminodiacetate ligand. Under physiological conditions, the hybrids selectively hydrolyze substrate DNA or RNA at the 3'-side of the sequence which is complementary with the DNA oligomers in the hybrids. The cerium(IV) ion is the most active as to DNA scission, whereas the europium(III), thulium(III), and lutetium(III) ions are the most effective for RNA scission. All the scissions proceed totally via hydrolysis of the phosphodiester linkages, in the same way as the scissions by natural nucleases and ribonucleases do. The artificial enzymes, which show far greater sequence-specificities than natural ones, exhibit high potential for application to molecular biology, biotechnology, and therapy.