DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 425

Table 12 . 23. Reduction potentials of some amino acids at pH 7; data taken from Milligan
et al. (2003)

Amino acid Reduction potential/V (vs NHE)

Cysteine + 0.92

Cystine + 1.1

Histidine + 1.17

Methionine + 1.5

Tryptophan + 1.03

Tyrosine + 0.93

This has been put forward as a possibility in many discussions for some time.
Yet, it is not a very convincing possibility. In recent years, the importance of the
complexity of DNA damage for an inadequate repair has been become apparent.
Clustered lesions increase the complexity of DNA damage, and most clustered
lesions involve O 2 . It is tempting to suggest that thiols interrupt at an early stage
the formation of clustered lesions and thus reduce the complexity of DNA dam-
age. It would be a major breakthrough in our understanding of the oxygen effect
if this question could be addressed experimentally.
DNA is typically surrounded by proteins, and the question obviously arises
as to what extent they may contribute to a repair of DNA radicals. The G • + /G •
radical has been generated in plasmid DNA in aqueous solution with the help of
(SCN) 2 • − , and the formation of G lesions has been monitored as SSBs induced by
the Fpg protein (Milligan et al. 2003). The repair of G • + /G • by electron-donating
amino acids has been studied. Most of these, notably tryptophan, were found to
be quite reactive except for histidine and some derivatives of cystine and me-
thionine (Table 12.23).
Attention has been drawn to the fact that the reduction potentials of the ami-
no acids in proteins may differ by -0.2 and +0.3 V from the above values, and
this may also inf luence the repair capability of proteins surrounding the DNA.
ET in DNA and proteins over a longer distance have been discussed above.
The phenolic catechins found in green tea are related to the phenol tyrosine,
and it hence not surprising that they also can repair some of the radical-induced
DNA damage in aqueous solution (Anderson et al. 2001). For being of any con-
sequence for DNA repair in vivo (as sometimes suggested), they would have to
accumulate near DNA, and this has not yet been shown to our knowledge.
The C

H BDE
(Chap. 7.4), and thermodynamically a reduction (by H-donation) of DNA radi-
cals by surrounding proteins is favored over a reduction by GSH and other thi-
ols. Yet, such H-donation reactions by peptides are kinetically disfavored. As a

H BDE of the peptide linkage in proteins is lower than the RS

− −