The Crystal Structure of 9-Ethyl-8-hydroxyguanine

Abstract

Analysis of the crystal structure of 9-ethyl-8-hydroxyguanine using X-ray diffraction showed that it is in C-8 keto form. As compared with 9-ethylguanine, significant differences were observed in bond lengths and bond angles of the imidazole ring.

NMR studies of a DNA containing 8-hydroxydeoxyguanosine

“…Although a keto-enol tautomerism is possible for the oh8G base, a keto form is predominant in the d(CGCoh8GAATT-CGCG) duplex. This is consistent with previous structural studies of 8-hydroxyguanine derivatives, such as 8-hydroxy-2'-deoxyguanosine (11), 8-hydroxyguanosine (12,13), and 9-ethyl-8-hydroxyguanine (14). For the oh8G:C base pairing, there are two possible base-pairing structures, which have different numbers of hydrogen bonds (Fig.…”

“…These results strongly suggest that the tautomer for the 8-hydroxyguanine base is a keto form in the d(CGCoh8GAATT-CGCG) duplex. This is consistent with the earlier observation that 8-hydroxyguanine takes a keto form in the 2'-deoxyribonucleoside (11), ribonucleoside (12,13), and 9-ethyl derivative (14). A comparison of the temperature dependence of the line widths (Fig.…”

“…Ab initio molecular orbital calculations have suggested that 6,8-diketo is the most energetically stable form of 8-hydroxyguanine (oh8G) (10). Structural studies of 8-hydroxyguanine derivatives, such as 8-hydroxy-2'-deoxyguanosine (11), 8-hydroxyguanosine (12,13), and 9-ethyl-8-hydroxyguanine (14), indicate that the predominant structure is a 6,8-diketo form for the base moiety and a syn form for the glycosidic conformation. Since the dominant tautomeric form of '8-hydroxyguanine' is a keto form, it may be called 8-oxo-7,8-dihydroguanine.…”

The role of 8-hydroxyguanine in carcinogenesis

“…The 6,8-diketo form of 8-OHG is in the lowest energy stage, i.e. the most stable form of the free nucleotide (19,20), and this is in accord with X-ray structural analysis of the ethyl analog, 9-ethyl-8-hydroxyguanine (21). The 6,8-diketo form is lower energetically but very near that of the 6-enol,8-keto form (Figure 1).…”

Base pairing of 8-oxoguanosine and 8-oxo-2'-deoxyguanosine with 2'-deoxyadenosine, 2'-deoxycytosine, 2'-deoxyguanosine, and thymidine

“…that a variety of chemical carcinogens can cause its formation (1,2). Recent investigations have focused on misreading of (3)(4)(5) and mutations caused by 8-oxomodified guanine bases (6)(7)(8), conformational changes caused by its presence in oligonucleotides (9,10), and studies of its structure (11)(12)(13)(14). These studies have shown that 8-oxoguanosine (8-OxoG)* 1 ****or 8-oxo-2'-deoxyguanosine occurs as the 6,8-diketo tautomer and that the conformation about the glycosidic bond is syn (14).…”