Guanine precursors

Figure 6 Biosynthesis of factor Z, an oxidation product derived from an intermediate in molydopterin biosynthesis. Biosynthetically equivalent positions in factor Z and guanine precursors are indicated the colored. For details, see text.

Studies with purine-deficient mutants narrowed the purine precursor down to a compound at the biosynthetic level of guanine. This implicated that the amino group of the cognate guanine precursor had to be replaced by oxygen in the course of biosynthesis. 

The two overwhelming oxidation products of the purine moiety of dGuo 37 arising from the transformation of guanine radical cations 38 were isolated and identified as 2,2-diamino-4-[(2-deoxy-/l-D-eryfhro-pentofura-nosyl)amino]-5(2H)-oxazolone (41) and its precursor 2-amino-5-[(2-deoxy-... 

Steenken et al. have concluded that in double-stranded DNA direct hydrogen atom abstraction from 2 -deoxyribose by G(-H) radical is very unlikely due to steric hindrance effects and a small thermodynamic driving force [94]. The EPR studies performed in neutral aqueous solutions at room temperature have shown that, in the absence of specific reactive molecules, the lifetime of the G(-H) radical in double-stranded DNA is as long as -5 s [80]. Therefore, the fates of G(-H) radicals are mostly determined by the presence of other reactive species and radicals. Thus, the G(-H) radical can be a key precursor of diverse guanine lesions in DNA. In the next section we begin from a discussion of the site-selective generation of the G(-H) radical in DNA, and then continue with a discussion of the reaction pathways of this guanine radical. 

Boehme, R.E. Phosphorylation of the antiviral precursor 9-(l,3-dihydroxy-2-propoxymethyl)guanine monophosphate by guanylate kinase isozymes. J. Biol. Chem., 259, 12346-12349 (1984)... 

Prakash Rao PJ, Bothe E, Schulte-Frohlinde D (1992) Reaction of dithiothreitol and para-nitroace-tophenone with different radical precursors of OH radical-induced strand break formation of single-stranded DNA in anoxic aqueous solution. Int J Radiat Biol 61 577-591 Prat F, Houk KN, Foote CS (1998) Effect of guanine stacking on the oxidation of 8-oxoguanine in B-DNA. J Am Chem Soc 120 845-846... 

Conventional chemistry converted carbinol 277 into acyl azide 278, which was treated under Curtius rearrangement conditions to obtain either amine 279 or urea derivative 280, the respective precursors of guanine derivative 281 and thymidine analogue 282. 

In abiotic conditions it has been possible to obtain all four RNA bases (adenine, cytosine, guanine and uracil), but not the DNA characteristic base (thymine). In vivo, furthermore, thymine is synthesised from uracil-based precursors. 

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