Nucleic Acids in Chemistry and Biology

the glycosylic bond of a 7-alkylguanine residue undergoes slow and spontaneous hydrolysis, and so creates
an apurinic site. This is a target for accurate repair (Section 8.11.2). In contrast, the cross-linking of two
neighbouring guanines at N-7 by a nitrogen mustard or equivalent bifunctional alkylating agent (e.g.cis-
platin, Section 8.5.4) is an important cell-killing event, and is equally significant for interstrand and
intrastrand cross-links.
3-Alkyladeninesare the major toxic lesion resulting from monofunctional alkylation of DNA. The alkyl
group lies in the minor groove of the DNA double helix where it can block the progress of DNA poly-
merases (Section 8.11.3). 3-Alkylguanineshave a similar physiological effect but are much less prevalent,
being formed ten times less frequently than 3-alkyladenines (Figure 8.11b). 1-Methyladenineand
3-methylcytosinealso block DNA replication.^85

324 Chapter 8

HN

N

Me

O

dR

HN

N

Me

O

O

dR

HN

N

Me

O

O

dR

OH

H

OOH

OOH

H

OH

HN

N

Me

O

O

dR

OH

O

dR NHCONH 2

HN

N

Me

O

O

dR

OH

H

OH

H

N

N

O

dR

O

Me

OH

HO

O 2

N

N

NH 2

O

dR

HN

N

O

O

dR

N

N

O

dR

NH 2

H

OH

N

N

O

dR

OH

H

OH

H

N

N

O

dR

O

H

OH

O

OH H^2 N

O

HO H

O 2

Figure 8.36 Products resulting from -radiolysis of deoxynucleosides in aerobic conditions

N

N

N

N

NH 2

dR

N

N

N

H

N

NH 2

dR

N

N

N

N

NH 2

dR

HO

H

OH

OH

N

N

N

NH

NH 2

dR

CHO

H

Figure 8.37 Major -radiolysis products from deoxyadenosine

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