N7-Methylguanine

Nucleic acids can contain of any one of three kinds of pyrimidine ring systems (uracil, cytosine, or thymine) or two types of purine derivatives (adenine or guanine). Adenine, guanine, thymine, and cytosine are the four main base constituents found in DNA. In RNA molecules, three of these four bases are present, but with thymine replaced by uracil to make up the fourth. Some additional minor derivatives are found in messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), particularly the N4,N4-dimethyladenine and N7-methylguanine varieties. 

For applications in the diagnostics and biomarker area, 8-oxo-7,8-dihydro-2,-deoxyguanosine (8-oxoGuo) was measured as an oxidation stress biomarker in urine samples from smokers and non-smokers (Hu et al. 2006). When 100, uL of samples (10 times dilution) were used, a detection limit of 5.7 pg/mL (2.0 fmol) was achieved. The cycle time was 10 min per sample. The application was used for clinical scale. A similar approach was used for the detection of N7-methylguanine, another carcinogen exposure biomarker in human urine (Chao et al. 2005). 

Tudek, B., Boiteux, S. Laval. J. (1992) Biological properties of imidazole ring-opened N7-methylguanine in MI3mpl8 phage DNA. Nucleic Acids Res., 20, 3079-3084... 

The bulk effect of water as a solvent is rather dramatic since it causes a drastic reduction of the nucleophilicity of 9-methyladenine N1 and even more of 9-methylguanine 06. As a result, there is a reversal of the nucleophilicity order of the purine bases passing from gas phase to aqueous solution. In fact, in solution, methyladenine is more nucleophilic than methylguanine. Moreover, oxygen and N7 nucleophilic centers of 9-methylguanine compete almost on the same footing in solution (Table 2.2) and also the reactivity gap between N1 and N7 of 9-methyladenine is highly reduced in comparison to the gas phase. 

A detailed theoretical analysis of the bonding situation in complexes of (NH3)3Ptn with 9-methylguanine and 9-methyladenine has revealed that electrostatics provide a larger contribution to the Pt N7(nucleobase) bond energy... 

Established cases of metal binding to the exocyclic amino groups of guanine bases are rare. Amino group mercuration has been reported for 1-methylguanosine (169e), and the X-ray crystal structure of a dianionic 9-methylguanine complex with Pt(II) at N7, and Hg(II) at both N1 and N2 has been determined (237). The compound has been depicted in Fig. 19. The pK values have not been determined. 

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