Synthesis of bis(guanidinylated-methylcytosine) and its effect toward nucleobase binding

Abstract

The synthesis, characterization, and binding interactions of novel 4-(bis(4,5-dihydro-1H-imidazole-2-yl)amino)-1-methylpyrimidin-2(1H)-one (compound A) with two i-motif forming DNA oligomers (telomeric and hypoxia-inducible factor 1 (HIF-1α) DNA sequences) is reported. DFT-D3 calculations are used to explore binding energies and structural bonding characteristics of compound A with various nucleobases and 1-methylcytosine. Results show a significant increase in DNA melting temperatures with the addition of compound A to both telomeric and HIF-1α DNA sequences. Other ligands have shown the ability to bind and increase i-motif stability. Compound A differs in that it possesses a modified cytosine base core, while lacking the ribose sugar to achieve a significant increase in the melting temperatures of both telomeric and HIF-1α sequences.