Psoralen‐Derivatized Oligothymidine Methylphosphonates form Triple Helices with DNA and Crosslink to a Specific Strand

Shwu‐Bin ‐B Lin*, Cheng-Wen Wu Lee

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Oligothymidine methylphosphonates derivatized at the 5′‐end with 4′‐aminoalkyl‐4,5′,8‐trimethylpsoralen (AMT) were prepared. The interaction of these oligonucleoside methylphosphonates with double‐stranded DNA was studied. Oligothymidine tnethylphosphonates, T7 and T14, were found to form triple helix with an oligodeoxyribonucleotide 45‐mer DNA duplex which contains an A15‐T15 sequence. Upon irradiation with 365 nm (UV light, AMT crosslinked to accessible thymidine residues in the target DNA. Both AMT‐derivatized T7 and T14 crosslink to the T15 containing strand of the double‐stranded DNA target, but they do not crosslink to the A15 containing strand which also contains a potential thymidine crosslinking site. Methylphosphonate oligomer, T7, was derivatized with AMT using either an ethyl‐, butyl‐ or hexyl‐linker. The efficiency of crosslinking is affected by the length of the aminoalkyl linker arm connecting the AMT to the methylphosphonate oligomer. The relative crosslinking efficiencies of the oligomers with these three types of linkers were different. Greatest crosslinking, 45%, was obtained using an oligomer having a butyl‐or a hexyl‐linker. The interaction of oligothymidine methylphosphonates with DNA can be enhanced by using two shorter AMT‐oligomers instead of using one full‐length AMT‐derivatized oligomer. This strategy was demonstrated by the interaction of AMT‐derivatized T7 with duplex DNA 35‐mer and 45‐mer target. The extent of crosslinking to the 45‐mer target, whose binding site can accommodate two molecules of AMT‐derivatized T7, is 45% whereas that with the 35‐mer target, which can accommodate only one T7 molecule, is only 3%. The results of our experiments suggest that AMT‐derivatized oligothymidine methylphosphonates can form triple‐stranded complex and psoralen photoadduct with DNA. The formation of such complexes may be useful in probing and controlling gene expression at the DNA level.

Original languageEnglish
Pages (from-to)963-967
Number of pages5
JournalJournal of the Chinese Chemical Society
Volume42
Issue number6
DOIs
StatePublished - 1 Jan 1995

Keywords

  • Oligonucleoside methylphosphonates
  • Psoralen
  • Triple‐stranded DNA

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