Themed collection Nucleic Acid Modifications

We review here the molecular mechanisms employed by DNMTs and TET enzymes that are responsible for shaping the DNA methylation pattern of a mammalian cell.

This review highlights the synthesis, biophysical properties, and wide range of applications of oligonucleotides modified with 2′-O-(pyren-1-yl)methyl-RNA monomers reported over the past 25 years.

The present review highlights recent progress in the synthesis of fluoro-modified nucleic acids, and their applications in diagnostics, and therapeutics, and as tools for probing the structure and function of nucleic acids by ¹⁹F NMR and MRI.

The ability of extended forms of 5-methylcytosine to direct DNA methylation by maintenance DNA methyltransferase was investigated.

We developed analogs of S-adenosyl-L-methionine with photo-caging (PC) groups and demonstrated enzymatic transfer and light-triggered removal based on a DNA-methyltransferase and plasmid DNA.

It may be useful to develop prodrugs that are selectively activated by oxidative stress in cancer cells to release cell-killing reactive intermediates.

DNA encoded ligands are self-assembled into bivalent complexes and chemically ligated to link their identities.

5-(Hydroxymethyl)uracil and -cytosine in DNA templates regulate transcription by bacterial RNA polymerase depending on the promoter, indicating that they may act as epigenetic marks.

A synthetic access to stable isotope modified large RNAs for structural biology is introduced.

Methods to map small-molecule binding sites on cellular RNAs are important for understanding interactions with both endogenous and exogenous compounds. Here, ‘Pt-Seq’ is presented as a high-throughput method to identify Pt adducts on RNA resulting from cisplatin treatment.

The structural basis for selective incorporation of BenziMP opposite O⁶-MeG by KlenTaq DNA polymerase is elucidated by X-ray crystallography.

Thermostable T7 RNA polymerase variants were explored for genetic alphabet expansion transcription involving the unnatural Ds–Pa pair.

The 10DM24 deoxyribozyme can site-specifically label RNAs with fluorophore-GTP conjugates. The phosphorothioate modification prevents enzymatic cleavage of the 2′,5′-branched RNA.

Sequencing-based profiling of spliceosomal snRNA demonstrates substoichiometric methylation at cap-proximal and internal sites that may impact splicing and protein production.

Lipidated peptide nucleic acids as tools for efficient liposome fusion at elevated temperatures – in a zipper and a double-zipper fusion design. An potent alternative to DNA-mediated membrane fusion.

A single phosphorodithioate in place of a phosphate in a 19mer hairpin-RNA regio-specifically boosts its affinity for MS2 phage coat protein.

Chemically modified aptamers have the opportunity to increase aptamer target binding affinity and provide structure–activity relationships to enhance our understanding of molecular target recognition by the aptamer fold.

We have demonstrated the synthesis of ONs containing 2′-Me-locked nucleotide analogous (X) and (Y), and examined their biophysical properties.

The emergence of the earliest nucleosides is an important, but unresolved, element of the origins of life that may have been facilitated by heterocycle reactivity and self-assembly.

The new semi-rigid spin label ^ImUm showed limited motion in RNA duplexes and accurate distances between two spin labels in RNA duplexes were obtained by pulsed EPR spectroscopy.

Structural information provides important insight to how major groove-modified triazole-containing siRNAs selectively knockout their intended target.

Transcriptome In Vivo Analysis (TIVA) probes capable of single cell mRNA isolation were generated with stabilizing oligonucleotide modifications, with the goal of enabling transcriptomic applications in a wide range of biological specimens.

Energetically activated double-stranded probes with interstrand arrangements of intercalator-functionalized nucleotides enable recognition of mixed-sequence DNA hairpins with excellent binding specificity.

Trastuzumab, an antibody prescribed for the treatment of metastatic breast cancer, was covalently conjugated to oligonucleotides and characterized by high resolution MALDI-ToF MS.

Highly efficient fusion and content mixing of liposomes encoded by lipidated oligonucleotides (LiNAs). “Hot fusion of biomembranes” – a low leakage process at elevated temperature.

A gold(I)-mediated reaction to a DNA-tagged spirocycle, and the tolerance of different nucleic acids to the reaction conditions are demonstrated.

Pseudouridine modifications in helix 69 of bacterial ribosomes impact aminoglycoside interactions by altering the RNA conformational states and accessibility to chemical probes.

8-Oxo-2′-deoxyguanosine in a tandem lesion context is two orders of magnitude more susceptible to oxidation than in a context of native DNA yielding hydantoin products.

Conformation of the alkylene lesion may play a role in interstrand cross-link repair by O6-alkylguanine DNA alkyltransferases.

BNAP-modified ODNs showed higher binding affinities toward complementary DNA and RNA as compared to ODNs bearing 2′,4′-BNA/LNA with 5-methylcytosine or 2′-deoxyribonucleoside with phenoxazine.

The Na⁺-specific Ce13d DNAzyme is rigid showing no global folding in the presence of Na⁺, but splitting it at the cleavage site enables its Na⁺-specific folding detected by FRET.

New phenothiazine-modified nucleotides were prepared and used for enzymatic synthesis of labelled DNA for electrochemical detection and redox coding of DNA bases.

Porphyrin-based photosensitisers and their DNA conjugates have been evaluated for interstrand crosslink generation using furan containing oligonucleotides and red light.

D-/L-Isonucleotides were used to explore the local conformation requirement at specific sites of siRNA; both silencing activity and nuclease resistant character were improved, respectively.

We have evaluated the possibility for using an imidazole modified nucleoside triphosphate for the enzymatic construction of artificial metal base pair with view on an expansion of the genetic code.