Methylated Adenines

Cleavage at A or G If the DNA is first treated with acid, dimethyl sulfate methylates adenine at the 3-position as well as guanine at the 7-position (not shown). Subsequent reaction with OH and piperidine triggers degradation and displacement of the methylated A or G purine base and strand scission, essentially as indicated here for reaction of dimethyl sulfate with guanine. 

Acid dissociation constants, UV and NMR spectral data for mono- and poly-N-methylated adenines 99H(51)2255. 

Chemistry of A, A, A -trimethyladenines and more highly N-methylated adenines 99H(51)1141. 

Small quantities of additional purines and pyrimidines occur in DNA and RNAs. Examples include 5-methyl-cytosine of bacterial and human DNA, 5-hydroxy-methylcytosine of bacterial and viral nucleic acids, and mono- and di-N-methylated adenine and guanine of... 

Sreerama N, Woody RW, Callis PR (1994) Theoretical study of the crystal field effects on the transition dipole moments in methylated adenines. J Phys Chem 98 10397-10407... 

Reaction between 79 and formamidine (Scheme 25) gave not 5-methyl-adenine (105), but a rearranged product (106). MINDO/3 calculations show that the two rings in 105 deviate considerably from coplanarity, with loss of conjugation and introduction of strain. Computed bond distances and... 

E. coli the methylase encoded by gene dam (Fig. 29-4), within 7 min of replication, methylates adenine at N-6 in the sequence GATC, which occurs at many locations.670 686 687 This methylation provides a label for the template strand in a newly replicated duplex. The GATC sites in the newly synthesized strand will not yet be methylated, and repair enzymes recognize it as the strand on which to carry out excision repair. Another system, which may function during recombination, acts on fully dam methylated DNA.655 Since eukaryotes do not use methylation of GATC sites to distinguish the old template and newly replicated DNA strands, other mechanisms must operate.669... 

A time-resolved ion yield study of the adenine excited-state dynamics yielded an excited-state lifetime of 1 ps and seemed to support the model of internal conversion via the nn state along a coordinate involving six-membered ring puckering [187]. In order to determine the global importance of the tict channel, a comparison of the primary photophysics of adenine with 9-methyl adenine will be useful, as the latter lacks a tict channel at the excitation energies of concern here. The first study of this type revealed no apparent changes in excited-state lifetime upon methylation at the N9 position [188] a lifetime of 1 ps was observed for both adenine and 9-methyl adenine. This was interpreted as evidence that the tict is not involved in adenine electronic relaxation. 

Figure 29. The TRPES spectra for adenine (left) and 9-methyl adenine (right), pumped at Xp mp = 267 nm and and probed at >,probe = 200 nm. The time dependence is plotted using a linear/ logarithmic scale with a linear scale in the region -0.4-1.Ops and a logarithmic scale for delay times 1.0-10.0 ps. See color insert.

Figure 30. Decay associated spectra for adenine (dashed lines) and 9-methyl adenine (solid lines), extracted from the 2D TRPES spectra using global fitting procedures. Both molecules were fit by the same two time constants ij <0.1 and 12 1.1 ps, agreeing quantitatively with previous results. The spectra, however, are very different for adenine as compared to 9-methyl adenine. For details, see the text. See color insert.

Although the time constants for adenine and 9-methyl adenine are very similar, the associated photoelectron spectra reveal important differences that are obscured in ion-yield measurements. The decay associated spectra obtained from the fitting algorithm are shown in Fig. 30. The spectra of the fast ( < 0.1 ps) components are shown for adenine (dashed green) and 9-methyl adenine (solid blue). Likewise, the spectra of the 1.1 ps components for adenine (dashed red) and 9-methyl adenine (solid black) are given. The electronic states of the cations are Do(ti 1), D (n x), and D2 (ti ). The expected Koopmans correlations would therefore be 7171 — Do(7i 1), D2(ti 1), and nn —> As... 

In Figure 31, we compare the associated spectrum of the fast component in 9-methyl adenine with calculated [194] Franck-Condon structures for the 7i7t —> Dq(n 1) +e (solid line) and 7171 —> Diin 1) + e (dash-dotted line) ionizing transitions. The two separated peaks agree well with the FC calculations, strongly suggesting that the short-lived state in 9-methyl adenine is the 7i7t state. By contrast, adenine contains an additional contribution that... 

Figure 31. Decay associated spectra of the short-lived state compared with calculated FC spectra for 9-methyl adenine (a) and adenine (b). In 9-methyl adenine, the nn — >o(ti-1),D2(ti-1) transitions leave a FC gap. In adenine, this gap is filled by the Tier ionizing transitions. See color insert.

Some organisms use this methylated adenine in place of adenine in their DNA. Explain how this affects the formation of base pairs. 

Methyl adenine [MEADEN02] (Fig. 15.19) was studied by neutron diffraction. In this unusually simple hydrogen-bond structure, there is a possible... 

The centrosymmetrical AA42 base pair is mostly observed in complexes 9-ethyl-8-bromo-adenine with 9-ethyl-8-bromo-hypoxanthine [EBAEBH1 9-methyl-adenine with l-methyl-4-thiouracil [SURMAD101 and with 2-thiohydantoin [BIFYOE] 9-ethyladenine with parabanic acid [EADPBA] 3-(adenin-9-yl)pro-piontryptamide [ADPRTR]. 

Fig. 18. The bond distances (A) and bond angles (degrees) in 2-thiouracil, 4-thiouraoil, and 2,4-dithiouracil, obtained by averaging of results from crystal structure containing the bases 2-thiouracil (cf. ref. 492), 4-thiouracil (1-methyl-thiouracil 9-methyl-adenine, 4-thiouridine hydrate, 1,- )3-Z)-arab-inofuranosyl-4-thiouracil, 3 -0-acetyl-4-thiothymidine 2,4-dithiouracil...

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). 

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