A double-headed nucleotide with two cytosines: DNA with condensed information and improved duplex stability

Kasper Beck, Charlotte Reslow-Jacobsen, Mick Hornum, Christian Henriksen, Poul Nielsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Double-headed nucleotide monomers are capable of condensing the genetic information of DNA. Herein, a double-headed nucleotide with two cytosine bases (CC) is constructed. The additional cytosine is connected through a methylene linker to the 2′-position of arabinocytidine. The nucleotide is incorporated into oligonucleotides and its effect on duplex stability is studied. For single incorporations, a thermal stabilization of 4.0 °C is found as compared to the unmodified duplex and it is shown that both nucleobases of CC participate in Watson-Crick base pairing. In combination with the previously published UT monomer, it is also shown that multiple incorporations are tolerated. For instance, a 16-mer sequence is targeted by a 13-mer oligonucleotide by using one CC and two UT monomers without compromising the overall duplex stability. Finally, the potential of double-headed nucleotides in triplex-forming oligonucleotides is studied, however, with the conclusion that the present design is not well-suited for this function.

Original languageEnglish
JournalBioorganic and Medicinal Chemistry Letters
Issue number5
Pages (from-to)740-743
Publication statusPublished - 1. Mar 2019



  • Double-headed nucleotides
  • Duplex
  • Nucleic acids
  • Oligonucleotides
  • Triplex

Cite this