Sequence-Specific Photocleavage of DNA by an Expanded Porphyrin with Irradiation above 700 nm

摘要

The development of chemically modified oligonucleotides as a means of regulating gene expression is a topic of current widespread interest. One approach being pursued involves using antisense agents containing photoactivatable groups. Such a strategem offers the advantage of providing sequence-specific reagents that are inert in the dark, yet subject to being "switched on" via irradiation at a particular wavelength. Currently, oligonucleotide conjugates containing azido derivatives, ellipticines, psoralens, proflavins, and porphyrin moieties are known. All of these derivatives modify DNA when irradiated at wavelengths below 700 nm. For use in vivo, however, photoactivation in the 700—900 nm region would be preferable as it is here that bodily tissues are most transparent. In this communication, we describe the photocleavage capabilities of two expanded porphyrins, the lutetium(III) texaphyrin complex (LuTx) 1 and the nonmetalated sapphyrin 4, both of which cleave DNA upon irradiation at wavelengths above 700 nm. The more efficacious of these two chromophores, LuTx 1, has also been incorporated into oligonucleotide conjugates (e.g., 3). The latter provide the first example of oligonucleotide-directed photocleavage of DNA with irradiation above 700 nm.