10.1002/chem.201802287
Chemistry - A European Journal
FULL PAPER
calculated for the ribulo nucleotides.25 Gamess2016 was used to
calculate electrostatic potentials at the 6-31G* level.26 Those potentials
were then converted into RESP atomic charges as described in Cieplak
et al.27
duplexes is significant from two aspects: a) ribuloNA is a highly-
destabilizing alternative backbone system with no self-pairing or
RNA/DNA cross-pairing capability,17 and, more importantly, b)
chimeric-backbone-heterogeneous RNA-DNA duplexes are
weaker than the corresponding homogeneous RNA or DNA
duplexes,37 even though RNA and DNA cross-pair efficiently
with each other. The latter aspect is also true for many of the
XNAs which base-pair with complementary RNA and DNA15 with
few exceptions.38 Considering these facts, the results presented
Acknowledgements
This work was jointly supported by NSF and the NASA
Astrobiology Program under the NSF Center for Chemical
here suggest an unusual design
–
that combining
Evolution, CHE-1504217.
We thank and Dr. Jayasudhan
oligonucleotide systems which do not pair with themselves or
cross-pair with others may lead to novel sequence-specific
pairing systems with more favorable functional profiles; while the
opposite seems to occur upon combining self- and cross-pairing-
capable systems. Governed by this trend and the relative
simplicity with which it can be employed, it is possible to
envision another dimension to expanding the repertoire of
modified nucleic acid backbones through varied combinations
employing non-functioning XNAs to fashion hybrid systems
(oligomers with heterogeneity in both their backbone and
nucleobase composition) with varied properties.
Yerabolu for providing isoGNA intermediates, Professors Reza
Ghadiri, Gerald Joyce, Nicholas Hud and our lab members for
helpful discussions and feedback. T. E. thanks the NASA
Astrobiology Postdoctoral Program for a fellowship. M.F. and
P.H. are indebted to the Fund of Scientific Research, Flanders
(contract FWO G0188) and to the KU Leuven (OT/14/128) for
financial support.
Keywords: Chimeric Nucleic Acid • RNA • DNA • XNA •
Oligonucleotides
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Oligonucleotide Synthesis: All modified oligonucleotides were
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phosphoramidite chemistry as described in the literature40 using slightly
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heating/cooling cycles. Oligonucleotide samples were further
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(CD) as outlined in the Supporting Information (Section 5.0).
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incubation in a 0.6% Human Serum buffer for 60 min. Nuclease activity
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Information, Section 6.0, for further details).
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submitted to conformational calculations using the Amber16 molecular
mechanics package.22 The ff99OL3 force field was chosen (parmbsc0
α/γ + χOL3 to ff99).23,
Additionally, RESP atomic charges were
24
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