9- Methyladenine

A very different but equally direct mechanism is used to repair 1-methyladenine and 3-methylcytosine. The amino groups of A and C residues are sometimes methylated when the DNA is single-stranded, and the methylation directly affects proper base pairing. In E. coli, oxidative demethylation of these alkylated nucleotides is mediated by the AllcB protein, a member of the a-ketoglutarate-Fe2+-dependent dioxygenase superfamily (Fig. 25-27). (See Box 4-3 for a description of another member of this enzyme family.)... 

FIGURE 25-27 Direct repair of alkylated bases by AlkB. The AlkB protein is an a-ketoglutarate-Fe2+-dependent dioxygenase. It catalyzes the oxidative demethylation of 1-methyladenine and 3-methyl-cytosine residues. 

Fig. 15.2 a -d. Formulas of some modified bases occurring naturally in transfer RNA s. a Hypo-xanthine, a guanine derivative lacking the 2-amino group b dihydrouracil and c 4-thiouracil, two derivatives of uracil d 1-methyladenine, a positively charged derivative of adenine... 

Thus in dimethylacetamide, methylation of 1-methyladenine with methyl p-toluenesul-fonate to give 1,9-dimethyladenine required 125 C/2 h whereas benzylation of 1-benzyl-adenine occurred at room temperature over 70 h (65JHC291). 

In this manner, 1-methyladenine and 1-methylhypoxanthine are synthesized. Alkylation of adenine with allyl bromide in dimethylacetamide in the presence of potassium carbonate gives 9-allyladenine (10a) which is rearranged to 9-prop-l-enyladenine (11a). Further alkylation with iodomethane gives l-methyl-9-prop-l-enyladenine (12a) which is subsequently cleaved to l-methyladenine (13a) by reaction with potassium permanganate. ... 

The Dimroth rearrangement is the most powerful reaction for the synthesis of Af -alkylat-ed adenines starting from N1 alkylated precursors. First observed on 1-methyladenine, which can be obtained from 2 -deoxy-l-methyladenosine by hydrolysis in acidic medium, the scope of this reaction has been greatly extended. The mechanism of this rearrangement has been elucidated, and is shown for the rearrangement of 1-methyladenine to A -methyl-adenine (29). 

G) 5-Methylcytosine (SMC) Hydroxymethylcyto-sine (HMC) 5-Carboxymethyl-deoxyuracil (5CMU) 5-(4, 5 -Dihydro-pentyl)deoxyuracil (SOMPU)" 1-Methyladenine (MA)... 

Several inhibitors are known that bind to the adenosine site of PARP (19). These inhibitors include 6-bromo-2 -deoxyuridine, caffeine, 5-bromouracil, diadenosine-tetraphosphate, 1-methyladenine, 5-nitrouracil, theophylline, theobromine, thymidine, and other compounds. These compounds are not as well studied as the nicotinamide analogs. In addition, it is not known whether these compounds can interact with the adenosine (A,) receptors that are involved in modulation of synaptic transmission and neuroprotective effects. 

These results obtained by Bartzsch et al. (1984) show in most cases only qualitative agreement with experimental relative tautomer energies in solution in that the calculated values exceed the experimental ones by up to a factor of 3. In the 1-methyladenine the good agreement between... 

Other protonated molecules may be similarly analyzed. Thus, it was shown that the m/z 150 ion did not correspond to N -methyladenine, but rather to its isomer, 1-methyladenine, which can be easily identified. At low temperatures, however, other a, b, c and d ions emerge and interfere (Fig. 102). 

These peaks disappear at higher temperatures. It was shown that adenine contained about 1% 1-methyladenine, which heretofore had never been detected. 

---