The nucleic-acid bases in DNA rely on hydrogen-bonding to maintain the structure that defines their function. When a hydrogen atom of a nucleic-acid base is substituted by a methyl-group the resulting change in sterics disrupts intrahelical and interstrand bonding, thus altering DNA structure and function. Substitutions on cytosine, as in the case of 5-methylcytosine and hydroxymethylcytosine, are the only known modified nucleic-acid bases that exist in eukaryotes, and both interfere with transcription of DNA. We model methylation on benzene and cytosine with and without a benzene in a sandwiched conformation using HCTH/6-31+g*.  This additional stacked benzene models both intercalation and the natural DNA environment. The methylation reaction is studied via Friedel-Crafts alkylation and via the reaction in the methyltransferase enzyme. Structures and energies are calculated for reactants, transition-states, and products. Results show that the presence of the stacked aromatic ring increases the energy of reaction and lowers the activation energy.

Model for methylation of cytosine: A potential marker for cancer

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.