Chemistry Reference
In-Depth Information
A
Cl
NH
3
Pt
H
3
N
NH
3
Cl
NH
3
=
Pt
G G
G G
Here,
B
Cl
NH
3
Pt
H
3
N
H
3
N
Cl
=
Pt
G N G
G N G
Here,
NH
3
N = A, C, T
C
H
3
N
=
Pt
C G N G
Here,
C G N G
NH
3
N = A, C, T
Cl/H
2
O
PG
D
Cl
NH
3
H
3
N
Pt
NH
3
H
3
N
Pt
NH
3
Pt
H
3
N
PG
deprotection
G
G
G
PG = protecting group
= oligonucleotide
Figure 9.4
Reactions of cisplatin with GG-containing oligonucleotides (A) and of transplatin
with GNG-containing chains (N = A, C, T) (B).
trans
-Pt(NH
3
)
2
1,3-chelates isomerize to 1,4-
chelates when the GNG sequence is fl anked by a 5
C (C). The reaction of guanine-containing
oligonucleotides with suitably protected platinum complexes affords platinated oligonucle-
otides with one labile bond (D)
′
nucleophiles that may render the complex unreactive before it reaches its target.
One solution envisages transplatin being replaced by a
trans
- (NH
3
)
2
platinum
complex in which the metal is linked to one labile substituent and a protecting group
selectively removable upon interaction with the target. However, this ideal protecting
group has not yet been discovered. So far, only thymine derivatives (Pt-
N
3 linkage)
have been used as protecting groups in the preparation of platinated oligonucle-
otides with one labile bond. Their use has not been extended, however, because they
are labile to acidic conditions that may induce depurination (Figure 9.4 D).
46,54
Over the years, chemists have applied various methods to clarify the structure
of platinated oligonucleotides. The presence of platinum had been assessed by
atomic absorption or induced coupled plasma mass spectrometry, but these tech-
niques were replaced by modern mass spectrometric techniques that allow the ioni-
zation of oligonucleotides, such as ESI or MALDI (ESI = electrospray ionization,
MALDI = matrix - assisted laser desorption ionization). The formation of a coordi-
nation compound was inferred from the evidence that reaction of the platinated
oligonucleotide with CN
−
or thiourea had afforded the nonmodifi ed chain. NMR
