The experimental and theoretical data indicates that DNA molecule can exist in different confirmations (B, Z, hairpins, etc.) and the nucleic acid bases (guanine, cytosine, adenine, and thymine) are capable of forming Watson-Crick, Hoogsteen, and 'wobble' base pairs. It has been proposed that the presence of tautomeric forms of bases can lead to spontaneous mutations due to the formation of Hoogsteen base pairs. Alternative explanation of transversion mutation is the formation of 'wobble' base pairs which does not require the presence of tautomers. The presence of different types of conformers and base pairs can lead to the changes in the overall structure of DNA molecules which can affect the information content of this molecule. Oligonucleotides can serve as model compounds in order to understand th molecular mechanism(s) which are responsible for spontaneous mutations. The purpose of this proposed work is to investigate and ascertain the presence and/or absence of Hoogsteen and 'wobble' base pairs in oligonucleotides by vibrational spectroscopic methods. It is well established that the solvent, pH, metal ions, base sequence, and substituents on nucleic acid bases can alter the primary and secondary structure of nucleic acids. Therefore, we propose to investigate the effects of pH, metal ions (monovalent and divalent), and base sequence on the formation of Hoogsteen and/or 'wobble' base pairs. Vibrational spectroscopic methods (Fourier transform infrared, Raman, resonance Raman, and FT Raman) will be employed to investigate the base pairing schemes and conformations of oligonucleotides in aqueous solution. This task will be accomplished by identifying and characterizing the absorptions (Raman and infrared) due to protonated species, tautomers, metal binding sites, backbone, and hydrogen bonds. Spectral subtraction techniques will be used to eliminate the contribution of solvent and individual oligonucleotides from the spectra. This method should yield the absorptions arising due to the formation of base pairs and structure of oligonucleotides from the changes in environment (pH, metal ions, and base sequence).
| Bayse, Gladys S; Hammonds-Odie, Latanya P; Jackson, Kimberly M et al. (2013) Permeation of roxarsone and its metabolites increases caco-2 cell proliferation. Adv Biol Chem 3:389-396 |
