Methylguanines

N-Methylcyclohexylamine, 13C NMR spectrum of, 954 1H NMR spectrum of, 953 Methylene group, 178 N-Methylguanine, electrostatic potential map of, 1121 6-Methyl-5-hepten-2-ol, DRPT-NMR spectra of. 451... 

Cornetta K, Croop J, Dropcho E, Abonour R, Kieran MW, Kreissman S, Reeves L, Erickson LC, Williams DA (2006) A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34-I- peripheral blood cells with 06-methylguanine DNA methyltransferase. Cancer Gene Ther 13 886-895... 

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. 

SCHEME 2.6 Reaction pathways for 9-methylguanine alkylation by o-QM, investigated by DFT. 

TABLE 2.3 Stability of the QM-9-Methyladenine and QM-9-Methylguanine Adducts (QM-A and QM-G, Respectively) Relatively to Reactants in the Gas Phase (AGgas) and in Aqueous Solution (AGaq). Activation Energies for Their Decomposition into Free QM and Cytosine (AG e )... 

Fig. 10 Bond lengths of a neutral and b radical cation, and c spin density mapping of AP-cyclopropy-N methylguanine radical cation optimized at the B3LYP/6-31G(d) level...

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). 

Although very well resolved experimental infrared spectra are available for the methylguanine molecule, it is difficult to make a comparison with our calculations, since two different tautomers of 9-methylguanine exist, and their frequencies are mixed in the experimental spectra [126], However, in general we can state that the agreement is good, even for the relative intensities. The spectrum is partially reported in Fig. 15. 

The vibrational spectrum of methylguanine-methylcytosine (GC) complex consists of 99 normal modes frequencies. Differently from the AT base pair, in the GC complex the normal modes of the two bases are coupled together, thus an analysis of the shift relatively to the isolated bases is extremely complicated. This stronger coupling can possibly he ascribed to the presence of three h-bonds, rather than two as in AT. However, we tentatively discuss some significant shifts. 

Figure 15. Selected frequency assignments for methylguanine, both in complex (top) and isolated (bottom). The values of the shift due to complexation are also given.

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