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Figure 7.5. Electrochemicaldiscriminationofsingle-nucleotidemismatch
with Fc-ODN: (a) probe hybridized to its complementary strand, (b) probe
hybridized to single-nucleotide mismatched strand, and (c) uncorrected
SWV profiles at the gold working electrodes modified with two different
fully matched duplexes (curves 1 and 3) and mismatched duplex (curve
2). Reproduced by permission from M. Inouye, R. Ikeda, M. Takase, and T.
Tsuri,J.Chiba, Proc. Natl. Acad. Sci. U.S.A. ,2005, 102 ,11606.Copyright2005
National Academy of Sciences, U.S.A.
π
A
-conjugated Fc-modified nucleoside analogue was connected at
the 5' end of single-stranded oligonucleotide. After hybridization to
the complementary strand, the 3' end of the probe DNA strand was
attached to goldelectrode by Au-thiolchemistry, Fig. 7.5.
Consequently the electrochemistry of the Fc marker can be
observed, allowing for the detection of complementary DNA. The
presence of a single-nucleotide mismatch in the duplex causes,
presumably, ablockage of the conduction pathway through the base
stack at the position of the base-pair mismatch. These results in a
dramatic reduction of the electrochemical response, see Fig 7.5c. In
addition, a comparison of different DNA probes containing an iso-
meric Fc-diamidopyridine conjugate for electrochemical mismatch
detection was carried out by the same authors in a separate study
[39]. It was concluded that despite different stereochemistries of
the Fc label, all conjugated DNA probes were capable of providing
satisfactory electrochemical response for mismatch discrimination.
In another study, anthraquinone monosulfonic acid (AQMS) was
employed as an electroactive intercalator allowing to differentiate
betweenacomplementarytargetDNAsequenceandonecontaining
either C-A or G-A single mismatches [40]. The electrochemistry
 
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