9128
C. J. Wilds et al. / Tetrahedron Letters 47 (2006) 9125–9128
0.3
0.25
0.2
CROSS-LINKED DUPLEX 9
NON-CROSS-LINKED CONTROL
0.15
0.1
0.05
0
20
30
40
50
60
70
80
90
Temperature (°C)
Figure 3. UV thermal denaturation profile of the cross-linked oligonucleotide 9 and non-cross-linked control duplex (50-dCGAAAGTTTCG)2.
ratio of the peak areas agrees with the nucleotide com-
position of the cross-linked oligonucleotide 9 (Table
1). MALDI-TOF mass spectral analysis of duplex 9
indicated a molecular weight of 6806.9 (expected
6805.4).
University for the critical proofreading of this
manuscript.
References and notes
1. Dronkert, M. L.; Kanaar, R. Mutat. Res. 2001, 486, 217–
247.
UV thermal denaturation studies were also carried out
on the cross-linked duplex 9 (Fig. 3). The cross-linked
duplex exhibited a single sigmoidal denaturation profile
characteristic of an oligonucleotide duplex with a melt-
ing temperature of 58 °C, an increase of 23 °C over the
corresponding, non-cross-linked control duplex. Part
of this stabilization could be entropic in nature as the
two stands are preorganized for complex formation.
2. (a) Ali-Osman, F.; Rairkar, A.; Young, P. Cancer
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In conclusion, a method to synthesize oligonucleotide
duplexes that contains an interstrand cross-link between
two deoxyguanosines at the O6-positions was devel-
oped. Solid-phase oligonucleotide synthesis yields suffi-
cient amounts of material with a high purity that
should allow for structural and biological studies.
7. Hayakawa, Y.; Kato, J.; Uchiyama, M.; Kajino, H.;
Noyori, R. J. Org. Chem. 1986, 51, 2400–2402.
8. Bis-phosphoramidite 6 was thoroughly characterized by
NMR and mass spectrometry analysis: ESI MS, M+Na+:
1926.5; 31P NMR, ppm, (acetone-d6), 154.74, 154.95, Rp/
Sp isomers.
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Acknowledgements
This work was supported by funding from the Natural
Sciences and Engineering Research Council of Canada
(NSERC), the Canada Foundation for Innovation
(CFI) and the Canada Research Chair (CRC) program.
We are also indebted to Ms. Margaret Wear and
Dr. Paul Miller at Johns Hopkins University for
MALDI analysis of the oligonucleotides, Mr. Nadim
Saade at McGill University for ESI-MS analysis of the
10. Zhu, Q.; Delaney, M. O.; Greenberg, M. M. Bioorg. Med.
Chem. Lett. 2001, 11, 1105–1107.
11. Noll, D. M.; Noronha, A. M.; Miller, P. S. J. Am. Chem.
Soc. 2001, 123, 3405–3411.
´
nucleosides and Dr. Sebastien Robidoux at Concordia