Chemistry Reference
In-Depth Information
T12
3'
Pt
A13
5'
G10
G22
A1
G2
G14
G21
G9
G3
G15
G8
G20
G4
A19
G16
T18
T5
T12
3'
Pt
A13
5'
G10
G22
A1
G2
G14
G21
G9
G3
G15
G8
G20
G4
A19
G16
T18
T6
T5
T17
Figure 7.10
Chemical formulae of two platinum-organic G-quadruplex binders that have
been shown to stabilize selectively and to bind covalently to G-quadruplexes. The proposed
binding mode on the antiparallel human telomeric G-quadruplex is indicated. For Pt-MPQ,
the binding and platination sites are located at both sides of the G-quadruplex,
127
whereas,
for Pt-ACRAMTU,
134
both sites are located at the same side of the G-quadruplex. Platination
sites are represented by circles
was found to be platinated, indicating that the guanines, even when they are thought
to be involved in the G-quartet, react more rapidly than adenines that are about
ten times less nucleophilic.
135
It is worth noticing that binding of the quinacridine
moiety on the 5
-end G-quartet cannot be excluded, but it would prevent the plati-
nation of the G-quadruplex, since no platinable guanines are available on the
opposite 3
′
- end.
78
Since the four adenines and some guanines of the fl exible G-quartets of the
human G-quadruplex structure are effi ciently platinated, the design of new plati-
num-hybrid compounds using different G-quadruplex binding motifs, represents an
exciting challenge. Preliminary studies with these conjugates have revealed interest-
ing biological responses worth further investigation.
′
