Unfolding of G-quadruplexes: Energetic, and ion and water contributions of G-quartet stacking

Chris M. Olsen, William H. Gmeiner, Luis A. Marky

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


It has been shown that DNA oligonucleotides composed, in part, of G repeat sequences can adopt G-quadruplex structures in the presence of specific metal ions. In this work, we use a combination of spectroscopic and calorimetric techniques to determine the spectral and thermodynamic characteristics of two DNA aptamers, d(G2T2G2TGTG2T 2G2), G2, and d(G3T2G 3TGTG3T2G3), G3; a sequence in the promoter region of the c-MYC oncogene, d(TG4AG3TG 4AG3TG4A2G2), NHE-III; and the human telomere sequence d(AG3T2AG 3T2AG3T2AG3), 22GG. The circular dichroism spectra of these oligonucleotides in the presence of K + indicate that all form G-quadruplexes with G-quartets in an antiparallel arrangement (G2), in a parallel arrangement (NHE-III and 22GG), or in a mixed parallel and antiparallel G-quartet arrangement (G3). Melting profiles show transition temperatures, TM, above 45 °C that are independent of strand concentration, consistent with the formation of very stable intramolecular G-quadruplexes. We used differential scanning calorimetry to obtain complete thermodynamic profiles for the unfolding of each quadruplex. Subtracting the thermodynamic folding profiles of G2 from those of G3 yielded the following thermodynamic profile for the formation of a G-quartet stack: ΔG°20 = -2.2 kcal/mol, ΔHcal = -14.6 kcal/mol, TΔScal = -12.4 kcal/mol, ΔnK+ = -0.3 mol of K+/mol, and Δnw =13 mol of H 2O/mol. Furthermore, we used this profile to estimate the thermodynamic contributions of the loops and/or extra base sequences of each oligonucleotide in the G-quadruplex state. The average free energy contributions of the latter indicate that the incorporation of loops and base overhangs stabilizes quadruplex structures. This stabilization is enthalpy-driven and is due to base-stacking contributions.

Original languageEnglish (US)
Pages (from-to)6962-6969
Number of pages8
JournalJournal of Physical Chemistry B
Issue number13
StatePublished - May 6 2006

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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