TRIPLEX FORMING OLIGONUCLEOTIDES CONTAINING POLYMERIC LINKERS

摘要

The present invention is an m-gap triplex forming oligonucleotide which comprises a first and second TFO. The two TFOs are connected by a chemical linker. Each TFO is capable of binding to a duplex DNA to form a triplex. The first TFO and the second TFO bind at sites in the duplex DNA which are contiguous. The chemical linker is of sufficient length to allow the first and second TFOs to bind to the duplex DNA at their appropriate sites. This m-gap TFO can be further enhanced by the addition of a DNA damaging agent. When the DNA damaging agent is attached to the chemical linker it provides site selective DNA damage to the duplex DNA upon formation of the triplex. The chemical linker can be any of a variety of polyethers or peptide linkers based upon proline II helix, other peptides, or other linear or branched polymers. DNA damaging agents are selected from psoralen and acridine derivatives, mustards, epoxides or bromoacetates. The m-gap TFO can be used in pharmacological doses for treatment of a variety of diseases in humans and animals. Any disease which is responsive to DNA damage can be treated.