Design and Synthesis of DNA-Cleaving Molecules

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There has been great interest in designing reagents that bind to DNA duplex selectively at desired sequences. Such molecules equipped with a chemical or photochemical tag capable of modifying or cleaving DNA at the site of binding should have great prospects as "synthetic artificial restriction enzymes" and not least as gene-selective drugs. We have focused on the use of natural DNA-binders such as antitumor antibiotics, DNA-binding proteins or sequence-defined oligonucleotides in combination with photoactivated DNA-cleaving molecules. We have succeeded in designing a new sequence specific "photochemical DNA cleaver" that binds specifically to-5'-GG-3'sequence. This molecule named as "photo-Fenton-reagent" is widely used as a convenient source of hydroxyl radical. We also succeeded in designing a different type of DNA-cleaving molecules based on the conceit obtained from the work on the action mechanism of ene-diyne type antitumor antibiotics such as neocarzinostatin or esperamicin.