Oligonucleotides are potent antioxidants acting primarily through metal ion chelation

Eyal Zobel, Eylon Yavin, Hugo E. Gottlieb, Meirav Segal, Bilha Fischer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


We report on a rather unknown feature of oligonucleotides, namely, their potent antioxidant activity. Previously, we showed that nucleotides are potent antioxidants in FeII/CuI/II-H202 systems. Here, we explored the potential of 2'-deoxyoligonucleotides as inhibitors of the Fe IIVCuI/II-induced OH formation from H2O 2. The oligonucleotides [d(A)5,7,20; d(T)20; (2'-OMe-A)5] proved to be highly potent antioxidants with IC 5o values of 5-17 or 4885 uM in inhibiting FeII/Cu II- or CuII-induced H2O2 decomposition, respectively, thus representing a 40-215fold increase in potency as compared with Trolox, a standard antioxidant. The antioxidant activity is only weakly dependent on the oligonucleotides' length or base identity. We analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry and 1H-NMR spectroscopy the composition of the d(A) 5 solution exposed to the aforementioned oxidative conditions for 4 min or 24 h. We concluded that the primary (rapid) inhibition mechanism by oligonucleotides is metal ion chelation and the secondary (slow) mechanism is radical scavenging. We characterized the CuI-d(A)5 and CuII-d(A)7 complexes by 1H-NMR and 31P-NMR or frozen-solution ESR spectroscopy, respectively. Cu 1 is probably coordinated to d(A)5 via Nl and N7 of two adenine residues and possibly also via two phosphate/bridging water molecules. The ESR data suggest Cu11 chelation through two nitrogen atoms of the adenine bases and two oxygen atoms (phosphates or water molecules). We conclude that oligonucleotides at micromolar concentrations prevent Fe II/CuI/II-induced oxidative damage, primarily through metal ion chelation. Furthermore, we propose the use of a short, metabolically stable oligonucleotide, (2'-OMe-A)5, as a highly potent and relatively long lived (t1/2 ∼ 20 h) antioxidant.

Original languageAmerican English
Pages (from-to)601-620
Number of pages20
JournalJournal of Biological Inorganic Chemistry
Issue number4
StatePublished - May 2010


  • Antioxidants
  • Cu fe
  • Epr spectroscopy
  • Oligonucleotides


Dive into the research topics of 'Oligonucleotides are potent antioxidants acting primarily through metal ion chelation'. Together they form a unique fingerprint.

Cite this