Nucleic Acids in Chemistry and Biology

ethoxyacrylyl-anthranilate moiety with downstream minor groove binding of a trisaccharide unit (Figure
8.27b).^60 Hydrogen atom abstraction follows the pattern H-5
H-1
, and this results in rather more sin-
gle than double strand cuts. Intercalative DNA binding has also been identified for the antibiotic C-1027
through a combination of hydrodynamic and spectroscopic studies.^61 Lastly, it seems likely that dynemicin
A also binds to DNA by a combination of intercalation and groove binding. It is activated by thiols (biore-
duction) or by light and also causes both single and double strand DNA cleavage.
The general mechanism of strand cleavage by removal of a 5
-hydrogen is common to all these antibio-
tics, as shown in Figure 8.28. Processes involving hydrogen atom abstraction from C-4
or C-1
are illus-
trated later (Section 8.9.1, Figure 8.35).

Covalent Interactions of Nucleic Acids with Small Molecules and Their Repair 315

O

O

PO 2

O

B

O 2 P

oxygen

capture

reduction

O

O

PO 2

O

B

O 2 P

O

O

PO 2

O

B

O 2 P

O

O

PO 2

O

B

O 2 P

O

OH

HO

O

O

B

O 2 P

O

O

PO 2

H

strand

scission

R

RH

Figure 8.28 DNA single-strand cleavage by 5
-hydrogen abstraction by an aryl radical, followed by oxygenation
and biological reduction

Figure 8.27 A superimposed set of NMR structures of the enediyne antibiotics (red) binding to DNA duplexes. In
each case the orientation of the macrocyclic enediyne is shown spanning the groove and saccharide
moieties buried deep in the minor groove. (a) Calicheamicin 1 I. (b) Esperamicin A showing intercalation
of the anthranilate moiety
(Adapted from Refs 58 and 60. © (1997), with permission from Elsevier)