Positively Charged Indolylmaleimides for the Repair of Cyclobutane Pyrimidine Dimers in DNA

Cyclobutane pyrimidine dimers (CPDs) in DNA are produced by UV photoirradiation. When electrons are supplied, these lesions are cleaved and can be converted back to native thymine bases. Electrons play a crucial role in the repair of CPDs. Five synthetic oligonucleotides harboring DNAs were synthesized and purified by reversed-phase HPLC. Efficient cleavage required a compound bearing both an electron donor and a positive charge. Indole is a strong electron donor, and the structures of unsymmetrical indolylmaleimides contain an indole moiety. Positively charged unsymmetrical indolylmaleimides generated via <i>N</i>-methylation of the quinoline ring were investigated for their ability to repair CPDs in double-stranded DNA. The fluorescence intensities of indolylmaleimides increased in the presence of double-stranded DNAs containing CPDs, testing binding interactions. The repair efficiency of these CPD-containing substrates was approximately 30% after 30 min of UV photoirradiation in the presence of indolylmaleimides. Extending photoirradiation to 60 min further increased the repair yield. A novel small-molecule was identified that efficiently repaired CPDs in double-stranded DNA.