Pyrimidine bases modification

FapyGua from isolated DNA, no further chemical modifications to the purine and pyrimidine bases have been observed (Halliwell and Aruoma, 1992). 

Zgierski MZ, Fujiwara T, Kofron WG, Lim EC (2007) Highly effective quanching of the ultrafast radiationless decay of photoexcited pyrimidine bases by covalent modification photophysics of 5,6-trimethylenecytosine and 5,6-trimethyleneuracil. Phys Chem Chem Phys 9 3206-3209... 

DNA at the sites where the restriction enzymes will act. Modification of host DNA is brought about by methylation of purine or pyrimidine bases. 

Figure 1.43 indicates major sites of reactivity within the ring structures for nucleophilic displacement reactions. Cytosine, thymine, and uracil all react toward nucleophilic attack at the same two sites, the C-4 and C-6 positions. The presence of powerful nucleophiles, even at neutral pH, can lead to significant base modification or cleavage with pyrimidine residues (Debye, 1947). For instance, hydrazine spontaneously adds to the 5,6-double bond, initiating further ring reactions,... 

As in the case of pyrimidine bases discussed previously, adenine and guanine are subject to nucleophilic displacement reactions at particular sites on their ring structures (Figure 1.50). Both compounds are reactive with nucleophiles at C-2, C-6, and C-8, with C-8 being the most common target for modification. However, the purines are much less reactive to nucleophiles than the pyrimidines. Hydrazine, hydroxylamine, and bisulfite—all important reactive species with cytosine, thymine, and uracil—are almost unreactive with guanine and adenine. 

In addition to the cutting and trimming of precursors by nucleases, extensive modification of purine and pyrimidine bases is required to generate mature tRNAs 235 Some of these modification reactions are... 

G and A (Fig. 12.7). Especially the 5-position of the pyrimidine DNA bases dU (and C) seems to be highly suitable for the attachment of electron donors since these base modifications can be regarded as unnatural and functionalized derivatives of the natural DNA base T. It is important to note that the design of this type of modification allows principally that the chromophores should point into the major groove of the DNA duplex while maintaining the natural Watson-Crick base pairing of the dU moiety to A as the counterbase in the complementary oligonucleotide strand. Hence this functionalization by the chromophores introduces only a local perturbation of the normal B-DNA conformation. 

More valuable information on nucleic acids has been obtained from pyrolysis data when it was possible to evaluate the nature and abundance of the purine/pyrimidine bases. The information on these bases is important for monitoring in vitro DNA synthesis [5,6], for the evaluation of chromosome modifications [7], and for the study of complex formation of DNA with cisplatin [11,12]. As indicated previously, the DIP technique was reported to be more useful for detecting the base component of the nucleic acid. However, some information on the bases can be obtained also by Curie point Py-MS, as it can be seen from the spectrum of NADPH (nicotinamide adenine dinucleotide phosphate) shown in Figure 13.2.3. The spectrum was obtained in similar conditions as spectra for DNA and RNA shown previously [8]. 

Novel congeners of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, 32), the dialkyl esters of purine and pyrimidine A-[2-(phosphonomethoxy)ethyl] derivatives substituted at position 2, 6 or 8 of the purine base (33) or position 2, 4 or 5 of the pyrimidine base (34), were prepared by alkylation of the appropriate heterocyclic base with 2-chloroethoxymethylphosphonate diester. Except for the 5-bromo-cytosine derivative (34a), no activity against DNA viruses or retroviruses was observed for the novel pyrimidine analogues. However, modifications to the purine led to compounds highly active against HSV-1 and -2, VZV, CMV, W, MSV and HIV. 

The type of base modification will determine which protein will come first and which system, BER or NER, will be used to cure the damaged DNA. NER is responsible for the removal of bulky adducts such as dimerized pyrimidine bases produced by UV radiation from sunlight, or benzo(a)pyren or psoralen adducts and others (Tab. 1). Bulky adducts are Table 1. Radiation-induced DNA damage recognition proteins in human cells. 

The base modifications discussed so far are mostly concerned with those permissible in the pyrimidine motif (Y RY). In the purine motif (R RY), the permitted triads are A-AT, T AT and G GC, and the following examples illustrate the permissible base modifications in this motif. 

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