Chemistry Reference
In-Depth Information
provides both proof of the presence of platinum (when the use of
195
Pt enriched
complexes allows
195
Pt spectra to be recorded) and, based on the comparison
between the chemical shifts of platinated and nonplatinated oligonucleotides, infor-
mation on the coordination point. This item of information, however, has also been
obtained from gel electrophoresis analysis after chemical reactions that modify
nonplatinated nucleobases and cleave the chain, and, more recently, from mass
spectrometric analysis after digestion with exonucleases. Both NMR and X-ray
crystallography provide structural information at the atomic level. The fi rst structure
was solved more than 10 years ago, and showed the distortion caused in a duplex
by the formation of a 1,2-intrachain
cis
- [Pt(NH
3
)
2
] adduct at a GG doublet.
55
High -
resolution pictures have also been obtained for duplexes with one strand coordi-
nated to other platinum complexes,
56,57
as well as for
cis
-
58
and
trans
- [Pt(NH
3
)
2
]
crosslinked duplexes.
51
9.3.2 Platination of Unprotected Oligonucleotides with an Appending
Chelating Group
The McLaughlin group explored the alternative of platinating oligonucleotides
incorporating an ethylenediamine group.
59,60
They introduced the phosphoramidite
derivative of the bis - Fmoc - protected chelator (Fmoc = 9 - fl uorenylmethoxycarbo-
nyl) at the 5
-end of an immobilized oligothymidine. After ammonia treatment and
purifi cation of the oligonucleotide derivative, reaction with K
2
PtCl
4
afforded the
expected dichloroplatinum(II) derivative. However, even though formation of a
chelate favours coordination with the diamine, the high reactivity of K
2
PtCl
4
pre-
cludes the inclusion of nucleobases other than thymine and thus limits the scope of
this approach (Figure 9.5 ).
′
NiPr
2
Fmoc
HN
N
P
OCNE
Fmoc
K
2
PtCl
4
H
2
N
NH
T
n
H
2
N
NH
T
n
HO
T
n
Pt
Cl
Cl
= solid matrix
Fmoc = 9-fluorenylmethoxycarbonyl
CNE = 2-cyanoethyl
Figure 9.5
Post-assembly platination of an oligonucleotide bearing an appending chelator
9.3.3 Solid - Phase Synthesis Using Platinated Building Blocks
Biopolymers, such as peptides and oligonucleotides, which are made up of the rep-
etition of a basic unit (amino acid or nucleoside, respectively), are commonly assem-
bled through solid-phase technologies. This process can be automated because the
