Chemistry Reference
In-Depth Information
Figure 5.14
Schematic representation of the reaction of G3 (d(A
1
T
2
G
3
G
4
G
5
T
6
A
7
C
8
C
9
C
10
A
11
T
12
)) with: (A) platinum complexes with secondary nitrogen donors having steric bulk (small
loops close to N) or (B) platinum compounds without steric bulk on the nitrogen atoms (Ref.
139 for related work)
The ' wrapped ' SS coil form becomes less stable in bip - Pt - G3 and Me
2
dab - Pt -
G3 adducts because the hydrophobic and bulky bip and Me
2
dab carrier ligands
prevent the fl anking regions of the negative DNA strand from approaching the
cationic Pt centre as closely as these regions can approach the Pt in adducts with
less hindered bis-ammine or primary diamine ligands. These effects involving the
bip and Me
2
dab ligands while destabilizing the 'wrapped' form, favour the duplex
form; therefore, the bip - Pt - G3 and Me
2
dab - Pt - G3 adducts with the crosslink in a
HH1 conformation favour the duplex form (Figure 5.14).
139
This is particularly true
for (
R,S,S,R
) confi guration of the diamine which induces the characteristic R canting
of platinated guanines in duplexes.
In the case of (
S,R,R,S
) confi guration of the diamine, the duplex appears to be
in equilibrium with a small amount of a single-stranded (most likely coil) form. The
facts that the (
S,R,R,S
) chirality favours L canting and that this canting is charac-
teristic of coils suggest a reasonable explanation for this result. An important
outcome of this investigation is that the conformation and annealing propensity of
SS oligonucleotides with G/G intrastrand crosslinks can be modulated by the stere-
ochemistry of the platinum carrier ligands.
5.6.4 Flexibility in Cisplatin Adducts with Double - Stranded Oligonucleotides
A few X-ray structures of double-stranded (DS) oligonucleotides containing a
cis
-
A
2
Pt moiety (A
2
= two ammines or a diamine) crosslinking two G residues of the
same strand
72,73,140,141
or of opposite strands
74
have been reported. In the intrastrand
