Chemistry Reference
In-Depth Information
Figure 9.16
Duplex formation between oligonucleotides selectively platinated at nucleo-
bases modifi ed with appending thioether and imidazole groups (X
S
and X
I
, respectively) and
the complementary chain promotes migration of platinum from sulfur to guanine (N7), and
crosslinks the two chains. (Adapted from
Angew. Chem. Int. Ed
., 2006,
45
, 8194-8197.)
Figure 9.17
Crosslinked duplexes can be obtained by reacting transplatin, an oligonucleotide
incorporating the X
S
and X
I
nucleobases at neighbouring positions and the complementary
chain. The metal links the imidazole ring and the N7 of the guanine opposite X
S
. (Adapted
from
Angew. Chem. Int. Ed
., 2006,
45
, 8194-8197.)
These results showed that this methodology
82,84
allowed targeting and cross-
linking of complementary oligonucleotides without sequence restriction, and they
opened up the possibility of using such platinated oligonucleotides in experiments
aiming at the control of gene expression, targeting either mRNAs or miRNAs.
The possibility of obtaining crosslinked duplexes without previous platination
of one of the two strands was also explored, as Orgel and collaborators had done
earlier.
88,89
One-pot crosslinking experiments were carried out by mixing equimolar
amounts of the modifi ed oligonucleotide, the complementary chain and transplatin
in duplex-forming conditions (Figure 9.17). The crosslinked duplex formed was the
same as in the previous experiments, which indicated that previous isolation of the
platinated modifi ed oligonucleotide was unnecessary. Moreover, the thioether-Pt-
imidazole chelate was always detected in the one-pot reaction mixture, which sug-
gested that its formation preceded that of the crosslinked duplex. The fact that no
