Organic Letters
Letter
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Figure 5. HPLC chromatograms before and after irradiation at 313 nm
of the indicated sequence and uracil as internal standard (70 μL, 200
pmol, PBS buffer pH 7.4).17
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(10) DEACM = 7-(diethylamino)coumarin-4-yl)methyl, NDBF =
NDBF = 1-(3-nitrodibenzofuran-1-yl)ethyl, NPP = 2-(o-nitrophenyl)
propyl), pHP = p-hydroxyphenacyl
formed T<>T dimers are no longer an issue: the additional caged
oligonucleotide whose sequence is shown in Figure 5, containing
several sequential deoxythymidines, was cleanly uncaged without
the formation of [2 + 2] photoproducts.17
In conclusion, we have presented two new nucleobase-caged
residues dTpHP and dTNDEACM. While the latter can be used with
regular solid-phase synthesis protocols for the former, the base-
free and protecting group-free protocols of Sekine had to be
used. Both residues show significantly different uncaging reaction
rates compared to their respective O4- and N3-caged counter-
parts. This made it possible to obtain four levels of sequential
uncaging in the same reaction solution using only two caging
groups and irradiating at two wavelengths for different amounts
of time. The new dTpHP residue can now be quantitatively
uncaged at 313 nm at reaction times which do not lead to
undesired [2 + 2] cycloaddition side products. Using the two
residues dTpHP and dTNDEACM, it was even possible to
orthogonally uncage the one or the other, albeit at the expense
of losing time-resolution due to the long uncaging times needed
for the latter residue. These new methods will increase the
versatility of the tool set of nucleobase-caged oligonucleotides
and will enable more complex light-regulation scenarios in the
future. Future experiments will show if this approach can be used
for biological applications.
(11) Rodrigues-Correia, A.; Weyel, X. M. M.; Heckel, A. Org. Lett.
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(12) Schafer, F.; Joshi, K. B.; Fichte, M. A. H.; Mack, T.; Wachtveitl, J.;
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(13) Sinha, R.; Hader, D. Photochem. Photobiol. Sci. 2002, 1, 225.
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(14) Mouret, S.; Baudouin, C.; Charveron, M.; Favier, A.; Cadet, J.;
Douki, T. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 13765.
(15) Ohkubo, A.; Seio, K.; Sekine, M. Tetrahedron Lett. 2004, 45, 363.
(16) Rodrigues-Correia, A.; Koeppel, M. B.; Schafer, F.; Joshi, K. B.;
̈
Mack, T.; Heckel, A. Anal. Bioanal. Chem. 2010, 399, 441.
(17) See our previous publication (ref 11) for examples for the
detection of cyclic pyrimidine dimers by RP-HPLC.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, technical details, and full spectroscopic
data for all new compounds. This material is available free of
AUTHOR INFORMATION
Corresponding Authors
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was made possible by funding through the Deutsche
Forschungsgemeinschaft (DFG). We gratefully acknowledge
support by M. Sekine and A. Ohkubo (Tokyo Institute of
Technology) by providing the required solid support for the
base-free solid-phase synthesis.
REFERENCES
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(1) (a) Gostl, R.; Senf, A.; Hecht, S. Chem. Soc. Rev. 2014, 43, 1982.
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(b) Szymanski, W.; Beierle, J. M.; Kistemaker, H. A. V.; Velema, W. A.;
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dx.doi.org/10.1021/ol502478g | Org. Lett. 2014, 16, 5128−5131