Photochemical generation of oligodeoxynucleotide containing a C4'-oxidized abasic site and its efficient amine modification: dependence on structure and microenvironment.
Bleomycin-induced oxidative DNA damage under limited oxygen conditions results in the formation of the C4'-oxidized abasic site (1). We synthesized the oligodeoxynucleotides (ODN) 5, which contains 4'-o-nitrobenzyloxythymidine (3), and 6, which contains 2-nitrobenzyloxy-4'-methoxy-2'-deoxy-d-ribofuranoside (4), as the caged precursors of 7, an ODN containing 1, to study its reactivity with amines. Photoirradiation of the single- and double-stranded 5 led to the formation of 7. Uncaging of the duplex was faster and the yield of 7 was higher with the double-stranded than with the single-stranded ODN. It was suggested that a low dielectric environment of the o-nitrobenzyloxy group in the minor groove of the duplex might accelerate the uncaging rate. Similarly, 6 and its duplex yielded 7 by photoirradiation. However, the yields of 7 were lower than those of 5, and duplex formation slowed the uncaging rate. Reaction of the obtained 7 with an amine resulted in the formation of the lactam 2b in good yield in both single- and double-stranded forms, showing that amine modification of biomolecules by an ODN containing 1 is possible under physiologic conditions.
Usui
Kazuteru
K
Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Aso
Mariko
M
Fukuda
Mitsuhiro
M
Suemune
Hiroshi
H
D000588:Amines / Q000737:chemistry* / Q000528:radiation effects*; D001665:Binding Sites; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects*; D010777:Photochemistry; D013997:Time Factors; D014466:Ultraviolet Rays
D000588:Amines; D009838:Oligodeoxyribonucleotides