Editorial
Introduction to the themed collection on XNA xeno-nucleic acids
Dennis Bong, Philip Holliger, and Chaoyong Yang introduce the RSC Chemical Biology themed collection on XNA xeno-nucleic acids.
Review Article
From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma
Nucleic acids have been extensively modified in different moieties to expand the scope of genetic materials in the past few decades, and engineered polymerases greatly facilitate their application in vitro and in vivo.
Review Article
Perspectives on conformationally constrained peptide nucleic acid (PNA): insights into the structural design, properties and applications
The performance of peptide nucleic acid (PNA) can be improved through a rational design strategy based on the incorporation of conformational constraint into the PNA backbone to pre-organize the PNA into the proper conformation.
Communication
Efficient synthesis and replication of diverse sequence libraries composed of biostable nucleic acid analogues
Blends of engineered polymerases enable efficient DNA-templated synthesis and reverse transcription of diverse-sequence oligonucleotide libraries composed of locked nucleic acid (LNA), 2′-O-methyl-RNA (2′OMe-RNA), or mixtures of the two.
Communication
Dependence of click-SELEX performance on the nature and average number of modified nucleotides
The click-SELEX procedure enables the identification of nucleobase-modified aptamers in which chemical entities are introduced by a copper(I)-catalysed alkyne-azide ‘click’ reaction.
Paper
Synthesis and structure–activity relationship of peptide nucleic acid probes with improved interstrand-crosslinking abilities: application to biotin-mediated RNA-pulldown
After optimization of interstrand crosslink reaction between furan-containing peptide nucleic acids and target oligonucleotides, the reversibility of the formed product is exploited for the pull-down of a sequence of interest from cell lysates.
Paper
Stimuli-responsive assembly of bilingual peptide nucleic acids
“Bilingual” biopolymers comprised of γ-modified peptide nucleic acids can harness peptide and nucleic acid codes to direct assembly and recognition. Herein, we demonstrate stimuli-responsive assembly through a toehold-mediated displacement motif.
Paper
Mutant polymerases capable of 2′ fluoro-modified nucleic acid synthesis and amplification with improved accuracy
Polymerases that have been evolved to synthesize 2′F XNA are often inaccurate. Here, we show that you can improve the accuracy of 2′F XNA polymerase synthesis by adding mutations previously found to improve the accuracy of natural DNA synthesis.
Paper
Covalently attached intercalators restore duplex stability and splice-switching activity to triazole-modified oligonucleotides
Oligonucleotides can bind to mRNA and alter gene expression, but require backbone modifications for clinical use. We show that attaching pyrene or anthraquinone to the ribose sugar next to an artificial triazole backbone restores duplex stability and splice switching ability in cells.
Paper
Conjugation of oligonucleotides with activated carbamate reagents prepared by the Ugi reaction for oligonucleotide library synthesis
A solution-phase conjugation method based on the Ugi reaction is reported, which enables the synthesis of an oligonucleotide-tagged peptoid library.
Paper
A ruthenium–oligonucleotide bioconjugated photosensitizing aptamer for cancer cell specific photodynamic therapy
Ruthenium complexes have emerged as a promising class of compounds for use as photosensitizers in photodynamic therapy. Direct conjugation to aptamers enhances their therapeutic usefulness by conveying specificity to Ru-mediated PDT.
Paper
Targeting a conserved structural element from the SARS-CoV-2 genome using L-DNA aptamers
In vitro selection was used to identify L-DNA aptamers with high affinity and selectivity for the s2m RNA structure in the SARS-CoV-2 genome.
About this collection
Nucleic acids not only form the basis of heredity but are potentially a source of novel nanostructures, nanodevices and powerful drugs. However, the functional scope of these is limited by systemic shortcomings in nucleic acid chemistry, which include a limited repertoire of chemical functionalities, poor chemical and biostability and a polyelectrolyte backbone, which dominates their physicochemical and pharmacological properties. This has spurred the development of chemically modified alternatives called Xeno-nucleic acids (XNAs), comprising alternative chemical configurations not found in nature to extend the chemical functional and informational scope of nucleic acids.
This themed collection, guest edited by Dennis Bong (Ohio State University), Philipp Holliger (MRC Laboratory of Molecular Biology), and Chaoyong Yang (Xiamen University), covers all aspects of modified nucleic acids in chemical and synthetic biology including both in vitro as well as in vivo applications, and new chemistries. Taken together, the papers collected in this themed collection represent the state of the art on XNAs and highlights work at the interface of chemistry and biology.