Aqueous Compatible Post-Synthetic On-Column Conjugation of Nucleic Acids Using Amino-Modifiers.

Nucleic acid conjugation methodologies involve linking the nucleic acid sequence to other (bio)molecules covalently. This typically allows for nucleic acid property enhancement whether it be for therapeutic purposes, biosensing, etc. Here, we report a streamlined, aqueous compatible, on-column conjugation methodology using nucleic acids containing a site-specific amino-modifier.

Preparation of 2-Aminoimidazole-Activated Substrates for the Study of Nonenzymatic Genome Replication.

Nonenzymatic genome replication is thought to be an important process for primitive lifeforms, but this has yet to be demonstrated experimentally. Recent studies on the nonenzymatic primer extension mechanism mediated by nucleoside 5'-monophosphates (NMPs) activated with 2-aminoimidazole have revealed that imidazolium-bridged dinucleotide intermediates (N*N) account for the majority of the chemical copying process. As a result, an efficacious synthetic pathway for producing substrates activated with an imidazoyl moiety is desirable.

Recommendations for Upper Limb Motor Recovery: An Overview of the UK and European Rehabilitation after Stroke Guidelines (2023).

Upper limb impairment is common after stroke, with a significant impact on the stroke survivor's function, social participation and quality of life. Clinical guidelines are needed to inform clinical practise, tailor interventions to improve outcomes and address unresolved research questions. This review contributes to the evidence guiding clinical practise for upper limb motor recovery after stroke by summarising the recommendations from the UK rehabilitation guidelines (National Institute for Health and Care Excellence (NICE) and the Intercollegiate Stroke Working Party (ISWP)) and the European Stroke Organisation (ESO) guidelines, all published in 2023.

Unusual Base Pair between Two 2-Thiouridines and Its Implication for Nonenzymatic RNA Copying.

2-Thiouridine (sU) is a nucleobase modification that confers enhanced efficiency and fidelity both on modern tRNA codon translation and on nonenzymatic and ribozyme-catalyzed RNA copying. We have discovered an unusual base pair between two 2-thiouridines that stabilizes an RNA duplex to a degree that is comparable to that of a native A:U base pair. High-resolution crystal structures indicate similar base-pairing geometry and stacking interactions in duplexes containing sU:sU compared to those with U:U pairs.

A Facile and General Tandem Oligonucleotide Synthesis Methodology for DNA and RNA.

Tandem oligonucleotide synthesis (TOS) is an attractive strategy to increase automated oligonucleotide synthesis efficiency. TOS is accomplished via the introduction of an immolative linker within a single sequence composed of multiple oligonucleotide fragments. Here, we report the use of a commercially available building block, typically utilized for the chemical phosphorylation of DNA/RNA oligomers, to perform TOS.