Photoswitchable formation of a DNA interstrand cross-link by a coumarin-modified nucleotide

Mohammad Mojibul Haque, Huabing Sun, Shuo Liu, Yinsheng Wang, Xiaohua Peng

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

A coumarin-modified pyrimidine nucleoside (1) has been synthesized using a CuI-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. A [2+2] cycloaddition reaction between a coumarin-modified pyrimidine nucleoside and the opposing thymidine, 2'-deoxycytidine, or 2'-deoxyadenosine on a DNA strand generates photoswitchable interstrand cross-links (ICLs) in the DNA.

Original languageEnglish (US)
Pages (from-to)7001-7005
Number of pages5
JournalAngewandte Chemie - International Edition
Volume53
Issue number27
DOIs
StatePublished - Jul 1 2014

Keywords

  • DNA cross-linking
  • click chemistry
  • cycloaddition
  • nucleosides
  • photoswitch

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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