Nucleic Acids in Chemistry and Biology

impaired by the presence of the third DNA strand.^74 Such psoralen-oligonucleotide conjugates are probes
for sequence-specific helix formation and may have application in site-directed mutagenesis or control
of gene expression.

8.8.3 Purine Photoproducts

Adenine and guanine are intrinsically more photostable than the pyrimidines and tend to transfer photo-
chemical excitation energy to neighbouring pyrimidines in DNA duplexes. However, UVB can lead to the
formation of adenine photoproductswith an adjacent adenine or thymine base (Figure 8.33a).^75 While the
quantum yields for these processes are low and product formation is easily quenched by base-pairing, the A–T
adduct has been shown to be mutagenic.
Of greater significance is the photo-oxidation of cellular DNA resulting from UVA irradiation involv-
ing an unidentified endogenous photosensitiser. The reactions result from one-electron oxidation or hydro-
gen abstraction (type I) or from singlet oxygen (type II) processes. The four bases are the preferred
substrates for type I reactions and reactivity depends on (low) ionisation potential in the order
GA
TC. Guanine products predominate because of ‘hole-transfer’ in dsDNA, by which radical
cation migration targets guanine, acting as a sink. Hydration of the initial guanine radical cation leads to
8-oxoguaninein an oxidative process or to FapyGuaby reduction. Alternatively, deprotonation of the gua-
nine cation radical leads to imidazolone and oxazolone products (Figure 8.33b). Lipscomb and Rich have
determined the X-ray structure of a DNA fragment containing 7,8-dihydro-8-oxoguanine (GO). The struc-
ture of the duplex form of d(CCAGOCGCTGG) has been determined to 1.6Å resolution. The 8-oxoGua
is in the anti-conformation and forms Watson–Crick base-pairs with the opposite C. There is no steric
clash of the 8-oxygen of G with backbone atoms.^76

320 Chapter 8

N

N N

N

NH 2

dR

N

N

dR

HN

N

CN

N

N

N

HN

NH

NH

N N

N NH 2

dR

OH

dR

HN

N

N

N

O

O

dR NNdR

NH 2

Me

a

H

P

P

H

HN

N N

N

O

H 2 N

dR

–e- HN

N N

N

O

H 2 N

dR

N

N N

N

O

H 2 N

dR

N

N

NH 2

O

HN N

O NH

2

O

HN

NH 2

HN

N N

N

O

H 2 N

dR

OH

H

HN

N N

H

N

O

H 2 N

dR

O

HN

N NH

CHO

H

N

O

H 2 N

dR

O 2

H 2 O

-H+

O 2

H 2 O

H 2 O

Imidazolone Oxazolone

8-OxoGuo

FapyGuo

b

Figure 8.33 (a) Structure of adenine-containing dimeric photoproducts. (b) Structure and mechanism of formation
of the type I photochemistry oxidation products of deoxyguanosine in DNA

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