Protonation of Nucleobases in Single- and Double-Stranded DNA

Julio C. González-Olvera, Matúš Durec, Radek Marek, Radovan Fiala, María del Rosario J. Morales-García, Eva González-Jasso, Reynaldo C. Pless

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Single-stranded model oligodeoxyribonucleotides, each containing a single protonatable base—cytosine, adenine, guanine, or 5-methylcytosine—centrally located in a background of non-protonatable thymine residues, were acid-titrated in aqueous solution, with UV monitoring. The basicity of the central base was shown to depend on the type of the central base and its nearest neighbours and to rise with increasing oligonucleotide length and decreasing ionic strength of the solution. More complex model oligonucleotides, each containing a centrally located 5-methylcytosine base, were comparatively evaluated in single-stranded and double-stranded form, by UV spectroscopy and high-field NMR. The N3 protonation of the 5-methylcytosine moiety in the double-stranded case occurred at much lower pH, at which the duplex was already experiencing general dissociation, than in the single-stranded case. The central guanine:5-methylcytosine base pair remained intact up to this point, possibly due to an unusual alternative protonation on O2 of the 5-methylcytosine moiety, already taking place at neutral or weakly basic pH, as indicated by UV spectroscopy, thus suggesting that 5-methylcytosine sites in double-stranded DNA might be protonated to a significant extent under physiological conditions.

Original languageEnglish
Pages (from-to)2088-2098
Number of pages11
JournalChemBioChem
Volume19
Issue number19
DOIs
StatePublished - 4 Oct 2018
Externally publishedYes

Keywords

  • DNA methylation
  • methylcytosine
  • nucleobases
  • oligonucleotides
  • protonation

Fingerprint

Dive into the research topics of 'Protonation of Nucleobases in Single- and Double-Stranded DNA'. Together they form a unique fingerprint.

Cite this