Solution structure and design of dithiophosphate backbone aptamers targeting transcription factor NF-κB

David E. Volk, Xianbin Yang, Susan M. Fennewald, David J. King, Suzanne E. Bassett, Sheela Venkitachalam, Norbert Herzog, Bruce A. Luxon, David G. Gorenstein

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


A variety of monothio- and dithiosubstituted duplex aptamers targeting NF-κB have been synthesized and designed. The specificity and affinity of the dithioate aptamers of p50 and RelA(p65) NF-κB homodimers was determined by gel shift experiments. The NMR solution structures for several unmodified and dithioate backbone modified 14-base paired duplex aptamers have been determined by a hybrid, complete matrix (MORASS)/restrained molecular dynamics method. Structural perturbations of the dithioate substitutions support our hypothesis that the dithioate binds cations less tightly than phosphoryl groups. This increases the electrostatic repulsion across the B-form narrow minor groove and enlarges the minor groove, similar to that found in A-form duplexes. Structural analysis of modeled aptamer complexes with NF-κB homo- and heterodimers suggests that the dithioate backbone substitution can increase the aptamer's relative affinity to basic groups in proteins such as NF-κB by helping to "strip" the cations from the aptamer backbone.

Original languageEnglish (US)
Pages (from-to)396-419
Number of pages24
JournalBioorganic Chemistry
Issue number6
StatePublished - Dec 2002
Externally publishedYes


  • Antisense
  • Dithioates
  • Monothioates
  • NF-κB
  • NMR
  • Solution structure

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery


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