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A normal duplex holds as many Watson-Crick base pairs as the number of nucleotides in its constituent strands. Here we establish that single nucleotides can be designed to functionally imitate dinucleotides without compromising binding affinity. This effectively allows sequence information to be more compact and concentrated to fewer phosphates.
Three 5-modified 2'-deoxyuridine nucleosides were synthesized and incorporated into oligonucleotides and compared with the previously published 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W. The introduction of an aminomethyl group on the phenyl group led to monomer X, which was found to thermally stabilize a 9-mer DNA:RNA duplex, presumably through the partial neutralization of the negative charge of the backbone. By also taking advantage of the stacking interactions in the major groove of two or more of the monomer X, an extremely high thermal stability was obtained. A regioisomer of the phenyltriazole substituent, that is the 5-(4-phenyl-1,2,3-triazol-1-yl)-2'-deoxyuridine monomer Y, was found to destabilize the DNA:RNA duplex significantly, but stacking in the major groove compensated for this when two to four monomers were incorporated consecutively. Finally, the 5-phenyl-2'-deoxyuridine monomer Z was incorporated for comparison, and it was found to give a more neutral influence on duplex stability indicating less efficient stacking interactions. The duplexes were investigated by CD spectroscopy and MD simulations.
Xeno nucleic acids (XNAs) are artificial genetic systems based on sugar-modified nucleotides. Herein, we investigate double-headed nucleotides as a new XNA. A new monomer, AT, is presented, and together with...
We investigated the potential of nucleobase-modified antisense oligonucleotides to induce exon-skipping, and found that 5-(phenyltriazol)-2′-deoxyuridine-modified antisense oligonucleotides induced efficient exon-skipping in vitro.
The solvatochromic fluorophore Nile Red, 9-diethylamino-5H-benzo[a]phenoxazine-5-one, is one of the most commonly used stains to enhance contrast of lipid-rich areas of microscopic biosamples. Quite surprisingly, relatively little is known about...
Nile Red is a benzo[a]phenoxazone dye containing
a diethylamino substituent at the 9-position. In recent years, it
has become a popular histological stain for cellular membranes and
lipid droplets due to its unrivaled fluorescent properties in lipophilic
environments. This makes it an attractive lead for chemical decoration
to tweak its attributes and optimize it for more specialized microscopy
techniques, e.g., fluorescence lifetime imaging or two-photon excited
fluorescence microscopy, to which Nile Red has never been optimized.
Herein, we present synthesis approaches to a series of monosubstituted
Nile Red derivatives (9-diethylbenzo[a]phenoxazin-5-ones)
starting from 1-naphthols or 1,3-naphthalenediols. The solvatochromic
responsiveness of these fluorophores is reported with focus on how
the substituents affect the absorption and emission spectra, luminosity,
fluorescence lifetimes, and two-photon absorptivity. Several of the
analogues emerge as strong candidates for reporting the polarity of
their local environment. Specifically, the one- and two-photon excited
fluorescence of Nile Red turns out to be very responsive to substitution,
and the spectroscopic features can be finely tuned by judiciously
introducing substituents of distinct electronic character at specific
positions. This new toolkit of 9-diethylbenzo[a]phenoxazine-5-ones
constitutes a step toward the next generation of optical molecular
probes for advancing the understanding of lipid structures and cellular
processes.
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