DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 413

Table 12 .16. Net charge ( Z ) dependence for the β values of the reduction in base release
by some thiols and disulfides. (Zheng et al. 1988)

β value/10 −3 mol dm −3

Compound Z at pH 7

Gua Thy Ade

2-Mercaptosuccinate −2 1.2 1.9 2.5

2-Mercaptoethanesulfonic acid −1 1.9 1.9

Glutathione (GSH) −1 1.2 3.0 1.8

2-Mercaptoethanol 0 1.8 4.3 4.1

1,4-Dithiothreitol 0 1.9 4.5 −

Cysteamine +1 4.0 7.0 8.0

WR 1065 +2 7.3 19 18

GSSG −2 0.4 0.9 0.8

Bis-2-hydroxyethyldisulfide 0 1.3 2.4 2.5

Cystamine +2 2.6 4.6 4.4

tightly bound to DNA, e.g., the bisbenzimidazole derivative Hoechst 33258 , the
high rate constant of the competitor may not be used for calculating the compe-
tition between DNA and the DNA-bound scavenger, because the tightly-bound
scavenger is now also subjected to the same non-homogeneous kinetics as DNA
(Adhikary et al. 1997a).

12 .11. 2
Thiols

With thiols, protection against free-radical attack and repair of DNA damage
(Sect. 12.12) is not always easy to disentangle in in vitro experiments and even
more so in cellular systems (e.g., Murray et al. 1990). This has to be kept in mind,
when some aspects of thiol protections are discussed here.
As in the case of poly(U), which has been studied as a model system in some
detail (Chap. 11.2), there is a relationship of the rate of protection of DNA by
thiols and disulfides and the charge of the sulfur compound due to ion con-
densation (for evidence of this phenomenon, see Smoluk et al. 1988b). As has
been measured by following the protection of DNA irradiated in aqueous solu-
tion against base release (Zheng et al. 1988), G (base release) follows the equation
G 0 / G p = 1 +

[RSH]. The data, compiled in Table 12.16, have been interpreted in
terms of electrostatic interaction of thiols of the thiols/disulfides with DNA lead-
ing to higher concentrations of cations with respect to neutral thiols/disulfides

β