Chemistry Reference
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An increased conformational flexibility of the ligand can increase the entropic pen-
alty for the formation of the ligand- and metal complex-modified duplex. However, an
inflexible linker may represent a steric barrier to the formation of the metal-containing
duplex.
In experiments by Brotschi et al. , a 19-bp DNA duplex with a central Bpy Bpy pair
in which the two Bpy were directly attached to the ribose was as stable as a 19-bp
duplex with a G
C pair in the place of the Bpy Bpy pair, although the two Bpy s cannot
form hydrogen bonds and are not complementary in shape [49]. In experiments by
Weizman and Tor, an 11-bp DNA duplex with a central Bpy Bpy pair in which the two
Bpy were attached to the ribose through a methylene linker was as stable as a 10-bp
duplex that had the same sequence but no Bpy Bpy pair, although in general extension
of a DNA duplex by a base pair leads to an increase in the duplex stability (Table 10.1,
entry 2) [11b]. These results suggest that the Bpy Bpy pair connected through the
methylene linkers to the duplex backbone has a lower stabilization effect than a Wat-
son-Crick base pair, and thus than a Bpy Bpy pair directly attached to the DNA back-
bone. It must nevertheless be noted that the effect of bipyridine substitution can be
modulated by the sequence and/or the length of the nucleic acid duplex as these param-
eters were different for the DNA duplexes used in the experiments by Weizman et al.
and by Brotschi et al. [11b,49].
2. The chemical nature of the nucleic acid influences the effect of a given ligand and
metal complex on the modified nucleic duplex.
For example, in experiments by Brotschi et al. and by Weizman et al. [11b,49], the
effect of a central Bpy Bpy pair on the DNA duplex stability was very small (see
above). In contrast, the effect of a central pair of the same ligands on a 10-bp Aeg-
based PNA duplex destabilized the duplex by more than 10 C [16a]. This difference
between the effect of Bpy in DNA and PNA correlates with the fact that central mis-
matches cause a significantly larger destabilization of PNA duplexes than of DNA
ones. In turn, this effect can be linked to the fact that DNA duplexes, which contain
strands with negatively charged backbones, are less stable than PNA duplexes with the
same sequence because the Aeg-based PNA has neutral strands (see Section 10.2).
3. The position of the ligand modification in the duplex, for example, in the center versus
close to the end of the duplex, can modulate the effect of the ligand substitution
because the relative contribution of central base pairs to duplex stabilization is higher
than that of terminal base pairs that are subject to fraying.
For example, the melting temperature for a 10-bp PNA duplex that contained a
Bpy Bpy pair close to the end of the duplex was almost the same as that of the duplex
that contained an AT base pair instead of the Bpy Bpy pair [16c]. In contrast, the melt-
ing temperature of the same duplex in which the Bpy Bpy pair was in the center of the
duplex was significantly lower than that of the non-modified duplex (Table 10.1,
entry 3) [16c].
4. The effect on duplex stability of a metal-containing, nucleic acid duplex can be
affected by the sequence and length of the nucleic acid.
It is well known that the melting temperature of nucleic acid duplexes and triplexes
increases with the length of these systems, which is due to cooperativity effects
between the nucleobase pairs, and with the increasing GC content of the duplexes. For
example, we observed that a palindromic, 8-bp PNA duplex was slightly more stable
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