The calculated base pairing energy of 8-oxoguanine in the syn–anti conformation with cytosine, thymine, adenine and guanine

详细信息    查看全文

• 作者：Reynisson ; J??hannes ; Steenken ; Steen
• 关键词：8-Oxoguanine ; DNA damage ; Base pairing energy ; Ionization potentials ; Mispairing and density functional theory
• 刊名：Journal of Molecular Structure: THEOCHEM
• 出版年：2005
• 出版时间：May 20, 2005
• 年：2005
• 卷：723
• 期：1-3
• 页码：29-36
• 全文大小：173 K

文摘

8-Oxoguanine (8OG) is a mutagenic oxidative product of guanine, which may serve as a mispairing lesion during DNA duplication. It can form syn–anti conformation with cytosine (C), thymine (T), adenine (A) and a syn–anti like base pair with guanine (G). Using the density functional theory (DFT) we calculated the base pairing energies of these species. The resulting energies are all approximately −10 kcal mol⁻¹, which is 15 kcal mol⁻¹ lower than for the classical Watson–Crick G–C base pair and the competing 8OG–C classical pair. According to this, 8OG syn–anti configuration is un-favored when it comes to base pairing but not impossible, explaining the lack of specificity of 8OG. Oxidation of 8OG–C and 8OG–A leads to a proton shift from 8OG⁺ to C and A, i.e. charge spin separation occurs. Furthermore, the oxidation event results in 20 kcal mol⁻¹ increase in the H-bond strength, which is again lost when the proton is removed from the N1-nitrogen of 8OG. All of the investigated base pairs form planar structures, in respect to the nucleotides making up the pairs, except 8OG–C that forms a 30° angle.