Journal of the American Chemical Society
COMMUNICATION
Table 1. Thermodynamic Data for Duplexesa
MALDI-TOF MS spectra, and CD spectra. This material is
’ AUTHOR INFORMATION
c,d
duplex
X:Y
Tm (°C)b
ꢀΔG°37
ꢀΔH° d
ꢀΔS° e
Corresponding Author
6 11
BF:BF
BF:A
BF:C
BF:G
BF:T
A:BF
C:BF
G:BF
T:BF
A:T
59.4 ((0.2)
62.2 ((0.3)
59.3 ((0.1)
56.5 ((0.1)
63.2 ((0.3)
60.4 ((0.7)
54.0 ((0.2)
56.4 ((0.2)
62.1 ((0.2)
64.5 ((0.2)
65.0 ((0.0)
52.6 ((0.2)
61.5 ((0.1)
50.0 ((0.0)
59.2 ((0.1)
56.5 ((0.2)
58.3 ((0.1)
55.2 ((0.1)
59.6 ((0.1)
15.8
18.0
16.9
14.9
19.1
15.9
12.0
14.5
16.7
19.9
19.0
12.6
17.4
11.5
16.3
14.5
15.5
13.8
16.0
110.0
128.0
127.0
109.1
137.0
106.9
69.9
303.0
355.0
355.0
304.0
380.0
294.0
187.0
286.0
304.0
393.0
352.0
241.0
341.0
211.0
330.0
293.0
306.0
273.0
310.0
3
6 12
3
6 13
’ ACKNOWLEDGMENT
3
6 14
3
We thank the National Institutes of Health for their generous
support (GM 069773), Andro C. Rios for input, and Mary Noꢀe
for assistance with MALDI experiments.
6 15
3
7 11
3
8 11
3
9 11
103.3
111.0
141.9
128.1
87.5
3
’ REFERENCES
10 11
3
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7 15
3
10 12
T:A
3
8 12
C:A
3
9 12
G:A
123.2
76.9
3
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8 15
C:T
3
9 15
G:T
118.8
105.5
110.3
98.4
3
7 13
A:C
3
7 14
A:G
3
10 13
T:C
3
10 14
T:G
112.0
3
a All samples contained 2.5 μM each strand of DNA, 20 mM Na
cacodylate, pH 7.0, 0.5 mM EDTA, and 100 mM NaCl. b Errors reflect
c
standard deviation derived from two individual experiments. (<0.3.
d Unit is kcal/mol. e Unit is cal/mol.
embedded between two pyrimidines (dC) when compared to
two purines (dG). Better base stacking within the G-BF-G
stretch (6 12ꢀ6 15, Table 1) likely results in more stable
3
3
duplexes compared to the corresponding C-BF-C duplexes
(7 11ꢀ10 11, Table 1). These observations are consistent with
3
3
reports showing inferior stacking interactions in C-2AP-C com-
pared to G-2AP-G, and with calculated thermal stabilities of
stacked DNA doublets, which predict that C-2AP is significantly
less stable than G-2AP when paired with G-T and C-T,
respectively.17b,21
Taking these results together, we conclude that the designed
bifacial nucleoside 3 performs as anticipated, generating stable
base pairs with both T and A within duplex DNA. While pairing
BF with T appears to be slightly favored over pairing with A, both
these matched pairs are more stable than the corresponding
mismatches with G and C. Intriguingly, a duplex containing a BF:
BF pair, although more stable than mismatched duplexes, shows
lower stability than “perfect” duplexes containing BF:A or BF:T
pairs. This is consistent with the stability differences observed
between the BF:A and BF:T pairs, as in a BF:BF pair one of the
nucleobases inevitably projects the 2AP face into the major
groove. It remains to be seen whether homopolymeric duplexes
containing nucleoside 3 would generate alternate or random
arrangements of the nucleobase BF.
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’ ASSOCIATED CONTENT
S
Supporting Information. Synthetic details, thermal dena-
turation measurements, van’t Hoff analyses, X-ray crystallography,
b
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dx.doi.org/10.1021/ja201397e |J. Am. Chem. Soc. 2011, 133, 6926–6929