Comprehensive study of the effects of methylation on tautomeric equilibria of nucleic acid bases.
Minor tautomers of nucleic acid bases can result by intramolecular proton transfer. These rare tautomers could be stabilized through the addition of methyl groups to DNA bases. A comprehensive theoretical study of tautomers of methylated derivatives of guanine, adenine, cytosine, thymine, and uracil was performed. Molecular geometries of all tautomers were obtained at the density functional theory and MP2 levels with the 6-31G(d,p) basis set, and single-point calculations were performed at the CCSD(T)/6-311G(d,p) level. Tautomers obtained by protonation at the preferred protonation site for methylated isolated bases were compared to their nonmethylated counterparts. The effects of methylation on the relative stabilities of nucleic acid base tautomers are also studied and discussed in this work. The results suggest that some sites on the bases may not be mutagenic and may even stabilize the canonical Watson-Crick form. The results also indicate that a number of methylation sites can stabilize the tautomers, suggesting possible mechanisms for mutagenic changes.
Forde
Gareth K
GK
Computational Center for Molecular Structure and Interactions, Jackson State University, Jackson, Mississippi 39217, USA.
Forde
Aviane E
AE
Hill
Glake
G
Ford
Adrian
A
Nazario
Alejandro
A
Leszczynski
Jerzy
J
D003198:Computer Simulation; D008745:Methylation; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D013237:Stereoisomerism
D009696:Nucleic Acids