Photoswitchable formation of a DNA interstrand cross-link by a coumarin-modified nucleotide.
A coumarin-modified pyrimidine nucleoside (1) has been synthesized using a Cu(I)-catalyzed click reaction and incorporated into oligodeoxynucleotides (ODNs). Interstrand cross-links are produced upon irradiation of ODNs containing 1 at 350 nm. Cross-linking occurs through a [2+2] cycloaddition reaction with the opposing thymidine, 2'-deoxycytidine, or 2'-deoxyadenosine. A much higher reactivity was observed with dT than dC or dA. Irradiation of the dT-1 and dC-1 cross-linked products at 254 nm leads to a reversible ring-opening reaction, while such phenomena were not observed with dA-1 adducts. The reversible reaction is ultrafast and complete within 50-90 s. Consistent photoswitching behavior was observed over 6 cycles of irradiation at 350 nm and 254 nm. To the best of our knowledge, this is the first example of photoswitchable interstrand cross-linking formation induced by a modified pyrimidine nucleoside.
Department of Chemistry and Biochemistry, University of Wisconsin Milwaukee, 3210 N. Cramer St., Milwaukee, WI 53211 (USA).
Mohammad Mojibul
MM
Haque
Huabing
H
Sun
Shuo
S
Liu
Yinsheng
Y
Wang
Xiaohua
X
Peng
D001483:Base Sequence; D057930:Click Chemistry; D003374:Coumarins / Q000737:chemistry*; D061565:Cycloaddition Reaction; D004247:DNA / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry; D003841:Deoxycytidine / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D013936:Thymidine / Q000737:chemistry; D014466:Ultraviolet Rays
D003374:Coumarins; D003839:Deoxyadenosines; D009838:Oligodeoxyribonucleotides; D011741:Pyrimidine Nucleosides; D003841:Deoxycytidine; D004247:DNA; C030123:coumarin; C058118:2'-deoxyadenosine; D013936:Thymidine
DNA cross-linking; click chemistry; cycloaddition; nucleosides; photoswitch