Chemistry Reference
In-Depth Information
O
O
S
S
N
N
A
N
O
O
N
(CH
2
)
n
NH
NH
O
O
(CH
2
)
n
N
N
N
N
B
N
O
O
N
N
O
O
N
O
O
C
D
HN
O
O
NH
(CH
2
)
3
NH
HN
(CH
2
)
3
(CH
2
)
n
(CH
2
)
n
Ph
N
E
2
+
N
N
M
= oligonucleotide chain
NH
HN
(H
2
C)
3
(CH
2
)
3
Figure 9.2
Alternatives to the crosslinking of two oligonucleotide chains by chemical deri-
vatization: disulfi de bridges (A), alkyl chains (B), stilbenes (C), phenantrenes (D) and metal
complexes (E)
Another alternative that has been pursued is that a metal atom, especially
platinum, could be made to establish the crosslink between the synthetic oligonu-
cleotide and the target. In the context of antisense, antigene or anti-microRNA
strategies, the platinum(II)-mediated attachment of small synthetic oligonucleotides
to their complementary targets (DNA or RNA) is expected to produce a more
persistent blockage than that obtained by simple hydrogen-bonding pairing.
In this chapter we review the attempts to achieve high therapeutic effi cacy as
a result of the formation of platinum crosslinks between oligonucleotide chains at
the duplex or triplex level. Over the past 15 years, a great deal of effort has been
devoted to the development of methodologies to synthesize platinated oligonucle-
otides, but the scope of applications of such molecules is limited because of the dif-
fi culties associated with their preparation (see Sections 9.3 and 9.4).
