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ChemComm
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DOI: 10.1039/C8CC06757K
COMMUNICATION
Journal Name
Table 1. Tm values for the CGG/CGG DNA in the absence or presence of ligands.a
attractive scenario for targeting not only the aberrantly
expanded CGG trinucleotide repeat but other repeats by small
molecules.
Added
TAb (°C–1
)
Tm (°C)
SD
∆
Tm (°C)
compound
–
0.010
0.013
0.010
0.018
0.027
32.6
54.6
56.4
66.2
58.0
2.5
0.3
0.1
0.2
0.7
–
NCD
22.0
23.8
33.6
25.4
Conflicts of interest
4 c
5 (+ 4) d
Dimer of 2 e
There are no conflicts to declare.
aUV-melting profiles for the 5 μM DNA 5’-(TCAA CGG TTGA)-3’/3’-(AGTT GGC
AACT)-5’ in the absence or the presence of each compound were measured in 10
mM sodium phosphate buffer (pH 7.0) containing 100 mM NaCl, and 0.1% Tween
Notes and references
1
2
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b
,
20. TA (Tangent Angle) is defined as the largest slope of the tangent of the Tm
c
profile. Condition A: NCD-CC (40 µM) was incubated at 37 °C for 18 h in
3
4
5
Y. Nadel, P. Weisman-Shomer and M. Fry, J. Biol. Chem.,
1995, 270, 28970–28977.
C. E. Pearson, K. N. Edamura and J. D. Cleary, Nat. Rev.
phosphate buffer (pH. 7.0, 10 mM), containing NaCl (100 mM), and 0.1% Tween
20. DNA was added just before Tm measurement.; d Condition B: NCD-CC (40 µM)
was incubated at 37 °C for 18 h in the presence of DNA (5 μM) in phosphate
e
Genet., 2005,
P. C. Gareiss, K. Sobczak, B. R. McNaughton, P. B. Palde, C. a.
6, 729–42.
buffer (pH. 7.0, 10 mM), containing NaCl (100 mM), and 0.1% Tween 20. data
was taken from ref. 18.
Thornton and B. L. Miller, J. Am. Chem. Soc., 2008, 130
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,
To examine if the dimer
5 undergo oligomerization on the
6
7
L. O. Ofori, J. Hoskins, M. Nakamori, C. A. Thornton and B. L.
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hairpin of d(CGG)9 repeat by the addition of external dithiol,
we briefly looked at the oxidation of NCD-CC in the presence
of dithioerythyritol. (Figure S6) Incubation of a mixture of NCD-
CC and
4
(containing a small amount of
5) (total 40 µM) with
M), however, did not change the
8
9
dithioerythyritol (160
µ
fraction of three compounds after 6 h. This preliminary study
suggested that precise design of thiol moiety regarding the
ease of intramolecular disulfide bond formation, the distance
of two thiols, etc. would be necessary to make the
oligomerization of thiol-modified CGG/CGG binding molecule
feasible on CGG repeat template.
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Figure 4. UV-melting profiles of the 5 μM CGG/CGG DNA in the presence or absence of
the 40 µM ligand; DNA only (black diamond); DNA with NCD (gray filled circle), 4
(condition A) (red filled circle), 5 (+4) (condition B) (blue filled circle).
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In conclusion, we have synthesized a newly functionalized
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Nucleic Acids Res., 2018, Epub ahead of print.
CGG/CGG binding molecule NCD-CC having
cysteinylcystein
moiety to undergo intramolecular disulfide bond formation or
intermolecular disulfide bond formation on CGG repeat DNA
template. Oligomerization of NCD-CC, however, was detected
neither under the similar conditions nor in the presence of
additional dithiol. As expected from our earlier studies, the
dimeric form of NCD-CC showed higher capability to stabilize
the CGG repeat hairpin supported that self-oligomerization of
CGG/CGG binding molecules on the CGG repeat is the
4 | J. Name., 2012, 00, 1-3
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