DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 396

base propenal originates from water (McGall et al. 1992). In this reaction the
2

C double bond of the base pro-
penal (Ajmera et al. 1986). The sequence (56) followed by (57) accounts for the
observation that stand breakage and H2

′ R -proton is eliminated when forming the C −

′ release precedes the formation of base

propenals.
The above scheme does not fully ref lect the present view expressed in the lit-
erature, 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

)-peroxyl radical reacts with O 2 • − , conditions that prevail formed when the C (4 ′

in the -radiolysis of DNA in oxygenated aqueous solution, but under these con-

ditions, no trace of base propenals is formed (Sect. 12.4.4). In early mechanistic
proposals, the geminal phosphatohydrine has been assumed to be an intermedi-
ate with the substantial lifetime of tens of minutes.

γ

Yet, the corresponding geminal chlorohydrines have a lifetime of less than a few
µs (Mertens et al. 1994). The related (i-PrO) 2 P(O)OC(CH 3 ) 2 OH decays with k ≥

10 4 s −1 , and the data on the peroxyl radical chemistry of trimethylphosphate
(Schuchmann, von Sonntag 1984) will have to be reinterpreted in so far as the
decay of (CH 3 O) 2 P(O)CH 2 OH into dimethylphosphate and formaldehyde must
have occurred during the bimolecular decay of the peroxyl radicals, i.e. on the
submillisecond time scale.

3 ×

12 .9. 3
Enediyne Antibiotics

The DNA-binding antibiotics, neocarzinostatin (NCS), dynemicin, calicheami-
cin and esperamicin have all in common that they have an enediyne as a struc-
tural element, although they are otherwise very different (for a review see Nico-
laou and Dai 1991). Their formulae are given in Fig. 12.13.
NCS intercalates with the aromatic moiety into the minor groove (Povirk et
al. 1981; Dasgupta and Goldberg 1985; for the kinetics with the model poly(dA-
dT) see Dasgupta et al. 1985) as do the other enediyne antibiotics, e.g., esperami-
cin (Yu et al. 1994). In the case of calicheamicin, the lifetime of the dihydrothio-
phene intermediate, formed in reaction (58), is sufficiently long to contribute to
the sequence-selective binding and thus to the observed cleavage pattern (Chat-
terjee et al. 1995).