Towards artificial repair of UV-damaged DNA: studies on drug binding and alkali hydrolysis.

Properties of the DNA containing the (6-4) photoproduct, one of the major UV-induced lesions, were analyzed. Two basic studies towards artificial recognition and repair of this type of damaged DNA are presented here. One is recognition of the UV-damaged DNA by a minor groove-binding drug. It was found by CD spectroscopy that distamycin could bind DNA duplexes containing the (6-4) photoproduct as effectively as the unmodified DNA, whereas a DNA duplex containing the cyclobutane pyrimidine dimer was not recognized by this drug. The other is a mechanistic study on alkali degradation of this photoproduct. HPLC and NMR analyses revealed that hydrolysis between the N3 and C4 positions of the 5' pyrimidine component occurred first. This intermediate was relatively stable, and further degradation to the strand break required severe conditions like the hot piperidine treatment.