Abstract
Among the natural bases, guanine is the most oxidizable base. The damage caused by oxidation of guanine, commonly referred to as oxidative guanine damage, results in the formation of several products, including 2,5-diamino-4H-imidazol-4-one (Iz), 2,2,4-triamino-5(2H)-oxazolone (Oz), guanidinoformimine (Gf), guanidinohydantoin/iminoallantoin (Gh/Ia), spiroiminodihydantoin (Sp), 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), urea (Ua), 5-guanidino-4-nitroimidazole (NI), spirodi(iminohydantoin) (5-Si and 8-Si), triazine, the M+7 product, other products by peroxynitrite, alkylated guanines, and 8,5′-cyclo-2′-deoxyguanosine (cG). Herein, we summarize the present knowledge about base pairs containing the products of oxidative guanine damage and guanine. Of these products, Iz is involved in G-C transversions. Oz, Gh/Ia, and Sp form preferably Oz:G, Gh/Ia:G, and Sp:G base pairs in some cases. An involvement of Gf, 2Ih, Ua, 5-Si, 8-Si, triazine, the M+7 product, and 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid (HICA) in G-C transversions requires further experiments. In addition, we describe base pairs that target the RNA-dependent RNA polymerase (RdRp) of RNA viruses and describe implications for the 2019 novel coronavirus (SARS-CoV-2): When products of oxidative guanine damage are adapted for the ribonucleoside analogs, mimics of oxidative guanine damages, which can form base pairs, may become antiviral agents for SARS-CoV-2.
Highlights
The DNA bases guanine, adenine, thymine, and cytosine have oxidation potentials of 1.29, 1.42, 1.6, and 1.7 V, respectively, and among them, guanine is most susceptible to oxidation [1]
The unidentified product having a mass corresponded to 7 amu (M+7) above that of guanine has been reported, and the M+7 product causes the greatest amounts of G-C transversions in addition to G-A transitions and G-T transversions [73]
T-705 ribofuranose, T-1106, ribavirin, N4−hydroxycytidine, and remdesivir can act as natural nucleosides in the RNA replication, and the fact that drugs with different structures have effects on RNA-dependent RNA polymerase (RdRp) of several viruses suggests that the nucleic acid derivatives capable of forming base pairs have broad-spectrum antiviral activities
Summary
The DNA bases guanine, adenine, thymine, and cytosine have oxidation potentials (vs. NHE) of 1.29, 1.42, 1.6, and 1.7 V, respectively, and among them, guanine is most susceptible to oxidation [1]. In the case of Klenow fragment exo-, cytosine, adenine, and guanine are incorporated opposite Gf. Human DNA polymerase κ incorporates guanine, cytosine, and adenine opposite Gf. When yeast DNA polymerase η is used, guanine and cytosine are incorporated opposite Gf. As a result of base incorporation, Gf is predicted to be able to form a Gf:G base pair with two hydrogen bonds (Figure 3B) [30]. SuperScript III incorporates guanine and adenine opposite both S-Sp and R-Sp [46] Based on these findings, Ia and Sp are oxidative guanine damages, which are involved in the generation of G-C transversions. The unidentified product having a mass corresponded to 7 amu (M+7) above that of guanine has been reported, and the M+7 product causes the greatest amounts of G-C transversions in addition to G-A transitions and G-T transversions [73]
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