The specificity and predictability of hybridization make
oligonucleotides
a powerful platform to program assemblies and networks with logic-gated
responses, an area of research which has grown into a field of its
own. While the field has capitalized on the commercial availability
of DNA oligomers with its four canonical nucleobases, there are opportunities
to extend the capabilities of the hardware with unnatural nucleobases
and other backbones. This Topical Review highlights nucleobases that
favor hybridizations that are empowering for assemblies and networks
as well as two chiral XNAs than enable orthogonal hybridization networks.
Pseudo-complementary oligonucleotides contain artificial
nucleobases
designed to reduce duplex formation in the pseudo-complementary pair
without compromising duplex formation to targeted (complementary)
oligomers. The development of a pseudo-complementary A:T base pair,
Us:D, was important in achieving dsDNA invasion. Herein,
we report pseudo-complementary analogues of the G:C base pair leveraged
on steric and electrostatic repulsion between the cationic phenoxazine
analogue of cytosine (G-clamp, C+) and N-7 methyl guanine
(G+), which is also cationic. We show that while complementary
peptide nucleic acids (PNA) form a much more stable homoduplex than
the PNA:DNA heteroduplex, oligomers based on pseudo-C:G complementary
PNA favor PNA:DNA hybridization. We show that this enables dsDNA invasion
at physiological salt concentration and that stable invasion complexes
are obtained with low equivalents of PNAs (2–4 equiv). We harnessed
the high yield of dsDNA invasion for the detection of RT-RPA amplicon
using a lateral flow assay (LFA) and showed that two strains of SARS-CoV-2
can be discriminated owing to single nucleotide resolution.
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