Base propenal

In strong base, propene reacts with chloroform to yield 2,2-dichloro-1 -methylcyclopropane. 

Dedon, P. C. Plastaras, J. P. Rouzer, C. A. Marnett, L. J. Indirect mutagenesis by oxidative DNA damage formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal. Proc. Natl. Acad. Sci. USA 1998, 95, 11113-11116. 

Table 3.18 contains data for three carbon bases propene, ethylene, and methane. The position of methane indicates that the saturated hydrocarbons, among the weakest of the Bronsted acids, are also among the weakest bases. The unsaturated hydrocarbons have electrons in higher energy orbitals and accept a proton more easily. There is information available, primarily from acidity function techniques, about solution basicities of a number of unsaturated hydrocarbons.104... 

Yermilov V, Rubio J, Ohshima H (1995) Formation of 8-nitroguanine in DNA treated with peroxyni-trite in vitro and its rapid removal from DNA by depurination. FEBS Lett 376 207-210 Yermilov V, Yoshie Y, Rubio J, Oshima H (1996) Effects of carbon dioxide/bicarbonate on induction of DNA single-strand breaks and formation of 8-nitroguanine, 8-oxoguanine and base-propenal mediated by peroxynitrite. FEBS Lett 399 67-70... 

Deoxyribose gives rise to TBA-reactive products (Halliwell 1990 Aruoma 1994 Loft and Poulsen 1999) which can be detected spectrophotometrically or by their fluorescence (Biaglow et al. 1997). However, the test is not specific [the reaction is also given by base propenals in the case of BLM action on DNA which is not OH-induced (Chap. 12) and can give misleading results (Gutteridge 1986) see also Draper et al. (1993)]. 

The hydroperoxide (two isomers) is formed in high yield under these conditions (the nature of the reduction equivalent that is required for this process is as yet not known), and subsequent treatment with a base gives rise to glycolic acid and the base propenal [Grob fragmentation reaction (292) yields near 90%]. 

According to the above scheme, there is a branching into a base propenal and malonaldehyde [reactions (30) and (31)]. In the radiolysis of DNA in aqueous solution, malonaldehyde is formed (see below), but there are practically no base propenals. On the other hand, in BLM-treated DNA, base propenals dominate. If these two products have the same precursor as in the above scheme, BLM still bound to DNA must catalyze reaction (30), while without this catalysis, reaction (31) must predominate. Experiments that could elucidate this point have not yet been carried out. 

In these experiments, the C(4 ) radical has been generated upon photolysis of the corresponding phenylselenide. The reducing agent in these experiments is as yet not ascertained. The base propenal was formed in high yields. This is in contrast to radiolytic experiments, where even with a large excess of (V- as a potential... 

Toeg 1982 Krushinskaya 1983 Kapp and Smith 1970 Ullrich and Hagen 1971 Janicek et al. 1985 Rashid et al. 1999). Nearly all the TBA-activity attributable to low-molecular-weight (DNA-free) material is due to malonaldehyde (Rashid et al. 1999), and there is no indication for the formation of base propenals which dominate the products of the BLM reaction (Sect. 12.9). Moreover, at low doses the major fraction is due to TBA-active material bound to DNA (Fig. 12.11). 

The formation of base propenals is not as straight-forward. From the above, it is clear that 02 is required for the formation of the base propenals. After the formation of the C(4 ) peroxyl radical [reaction (53)], the Fe(IV)BLM species has to interact with this peroxyl radical, possibly by forming an adduct [reaction... 

The latter then decomposes and subsequently yields the products, the 3 -phosphoglycolate, the base propenal and the 5 -phosphate terminus [reactions... 

The above scheme does not fully reflect the present view expressed in the literature, but retains essential elements. In the literature one usually finds as one of the intermediates the 4 -hydoperoxide. This is a species that should also be formed when the C(4 )-peroxyl radical reacts with 02, conditions that prevail in the y-radiolysis of DNA in oxygenated aqueous solution, but under these conditions, no trace of base propenals is formed (Sect. 12.4.4). In early mechanistic proposals, the geminal phosphatohydrine has been assumed to be an intermediate with the substantial lifetime of tens of minutes. 

Ajmera S, Wu JC, Worth J, Rabow LE, Stubbe J, Kozarich JW (1986) DNA degradation by bleomycin evidence for 271-proton abstraction and for C-O bond cleavage accompanying base propenal formation. Biochemistry 25 6586-6592... 

McGall GFI, Rabow LE, Ashley GW, Wu SH, Kozarich JW, Stubbe J (1992) New insight into the mechanism of base propenal formation during bleomycin-mediated DNA degradation. J Am Chem Soc 114 4958-4967... 

Wu JC, Kozarich JW, Stubbe J (1985a) Mechanism of bleomycin evidence for a rate-determining 4 -hydrogen abstraction from poly(dA-dU) association with the formation of both free base and base propenal. Biochemistry 24 7562-7568... 

Figure 5 Examples of DNA single strand breaks produced upon OH-mediated hydrogen abstraction to the 2-deoxyribose moiety. Attack at the H4 position induces the release of base propenal and the formation of phosphoglycolate, while abstraction of H5 leads to theformation ofa. t alcJehyde.

Zhou, X., Taghizadeh, K., and Dedon, P.C. (2005) Chemical and biological evidence for base propenals as the major source of the endogenous M, dG adduct in cellular DNA. /. Biol. Chem., 280, 25377-25382. 

Plastaras, ).P., Dedon, P.C., and Marnett, L.). (2002) Effects of DNA structure on oxopropenylation by the endogenous mutagens malondialdehyde and base propenal. Biochemistry, 41, 5033-5042. 

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