Chemistry Reference
In-Depth Information
Pt
O
O
N
N
NH
NH
O
N
O
N
N
NH
PG
Platinum(II) complex
N
NH
PG
O
O
(at least one
labile bond)
PG = protecting group
O
O
N
O
O
N
N
Platinum(II) complex
O
N
N
NH
PG
O
(at least one
labile bond)
O
PG = protecting group
Figure 9.7
N2-protected guanines react with platinum complexes, but protection of the O6
with a bulky group prevents platination at the N7 position
showed that fully protected oligonucleotides reacted very slowly with platinum(II)
complexes. The yield of the platination reaction increased when the phosphate
protecting groups were removed, which was associated with favourable electro-
static interactions between the positively charged cation and negatively charged
phosphates.
The proof of concept was obtained when different 2
- deoxyhexanucleotides
were selectively platinated at the guanines whose
O
6-position had been left unpro-
tected (Figure 9.7).
69
The oligonucleotide chains were assembled on controlled pore
glass (CPG) using an oxalyl linker and either the standard phosphoramidite deriva-
tives (T, A
Bz
, C
Bz
, G
iBu
, where Bz = benzoyl, iBu = isobutiryl) or the
N
2 - propanoyl,
O
6 -
diphenylcarbamoyl phosphoramidite derivative of guanine. Cleavage and removal
of phosphate-protecting groups afforded the desired partially protected oligonucle-
otide, which reacted regioselectively with [Pt(en)Cl
2
] (en = 1,2 - diaminoethane). The
target platinated oligonucleotide was obtained after removal of nucleobase protect-
ing groups with concentrated aqueous ammonia. Although the authors suggested
that this approach might be used for the generation of other site-specifi cally plati-
nated oligonucleotides, such as
trans
- Pt - 1,3 - GNG adducts, this alternative has not
yet been explored.
Moreover, this alternative seems to be restricted to the preparation of plati-
nated oligonucleotides with no labile platinum-ligand bonds, unless a platinum
protecting group is made available that is stable to ammonia, but removable under
conditions that do not damage the oligonucleotide.
′
