Advances in Nucleic Acid Research: Exploring the Potential of Oligonucleotides for Therapeutic Applications and Biological Studies.

In recent years, nucleic acids have emerged as powerful biomaterials, revolutionizing the field of biomedicine. This review explores the multifaceted applications of nucleic acids, focusing on their pivotal role in various biomedical applications. Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), possess unique properties such as molecular recognition ability, programmability, and ease of synthesis, making them versatile tools in biosensing and for gene regulation, drug delivery, and targeted therapy.

Novel Combination of Surface Markers for the Reliable and Comprehensive Identification of Human Thymic Epithelial Cells by Flow Cytometry: Quantitation and Transcriptional Characterization of Thymic Stroma in a Pediatric Cohort.

Thymic epithelial cells (TECs) are essential in supporting the development of mature T cells from hematopoietic progenitor cells and facilitate their lineage-commitment, proliferation, T-cell receptor repertoire selection and maturation. While animal model systems have greatly aided in elucidating the contribution of stromal cells to these intricate processes, human tissue has been more difficult to study, partly due to a lack of suitable surface markers comprehensively defining human TECs. Here, we conducted a flow cytometry based surface marker screen to reliably identify and quantify human TECs and delineate medullary from cortical subsets.

Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland.

Background: In December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now named B.1.1.

Study of Ground State Interactions of Enantiopure Chiral Quaternary Ammonium Salts and Amides, Nitroalkanes, Nitroalkenes, Esters, Heterocycles, Ketones and Fluoroamides.

Chiral phase-transfer catalysis provides high level of enantiocontrol, however no experimental data showed the interaction of catalysts and substrates. H NMR titration was carried out on Cinchona and Maruoka ammonium bromides vs. nitro, carbonyl, heterocycles, and N-F containing compounds.

Paper-based electrochemical peptide sensor for on-site detection of botulinum neurotoxin serotype A and C.

Botulinum neurotoxins (BoNTs) produced by soil bacterium Clostridium botulinum are cause of botulism and listed as biohazard agents, thus rapid screening assays are needed for taking the correct countermeasures in a timely fashion. The gold standard method relies on the mouse lethality assay with a lengthy analysis time, i.e.

Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: An and Experimental Integrated Approach.

In the present work, structural features of the interaction between peptide nucleic acid (PNA)-based analogs of the tumor-suppressor microRNA-34a with both its binding sites on MYCN mRNA were investigated. In particular, the region from base 1 to 8 ("seed" region) of miR-34a was reproduced in the form of an 8-mer PNA fragment (tiny PNA), and binding to target 3'UTR MYCN mRNA, was studied by a seldom reported and detailed NMR characterization, providing evidence for the formation of anti-parallel duplexes with a well-organized structural core. The formation of PNA-3'UTR duplexes was also confirmed by Circular Dichroism, and their melting curves were measured by UV spectroscopy.

Paper-based electrochemical peptide nucleic acid (PNA) biosensor for detection of miRNA-492: a pancreatic ductal adenocarcinoma biomarker.

Pancreatic ductal adenocarcinoma is the predominant neoplastic disease of the pancreas and it represents the fourth most frequent cause of death in cancer-related disease, with only 8% of survivors after 5-year to the diagnosis. The main issues of this type of cancer rely on fast progress (i.e.

Novel atrazine-binding biomimetics inspired to the D1 protein from the photosystem II of Chlamydomonas reinhardtii.

Biomimetic design represents an emerging field for improving knowledge of natural molecules, as well as to project novel artificial tools with specific functions for biosensing. Effective strategies have been exploited to design artificial bioreceptors, taking inspiration from complex supramolecular assemblies. Among them, size-minimization strategy sounds promising to provide bioreceptors with tuned sensitivity, stability, and selectivity, through the ad hoc manipulation of chemical species at the molecular scale.

First enantioselective synthesis of gingesulfonic acids and unequivocal determination of their absolute stereochemistry.

Herein we report the first organocatalysed enantioselective synthesis of gingesulfonic acids and shogasulfonic acids via a mild and convenient aminothiourea-catalysed conjugate addition of bisulfite to the olefin moiety of α,β-unsaturated carbonyls-a technology previously reported by us. A series of optically active naturally occurring sulfonic acids are prepared in their natural and unnatural configurations, and their absolute configurations are unequivocally confirmed by single crystal X-ray diffractometry.

A combined experimental and computational study on peptide nucleic acid (PNA) analogues of tumor suppressive miRNA-34a.

MicroRNAs are a ubiquitous class of non-coding RNAs able to regulate gene expression in diverse biological processes. Widespread miRNAs deregulation was reported in numerous diseases including cancer, with several miRNAs playing oncogenic and/or tumor suppressive role by targeting multiple mRNAs simultaneously. Based on these findings, miRNAs have emerged as promising therapeutic tools for cancer treatment.

Periodontal bacterial supernatants modify differentiation, migration and inflammatory cytokine expression in human periodontal ligament stem cells.

Periodontal ligament stem cells (PDLSC) play an important role in periodontal tissue homeostasis/turnover and could be applied in cell-based periodontal regenerative therapy. Bacterial supernatants secreted from diverse periodontal bacteria induce the production of cytokines that contribute to local periodontal tissue destruction. However, little is known about the impact of whole bacterial toxins on the biological behavior of PDLSC.

Enantioselective cyclopropanation of (Z)-3-substituted-2-(4-pyridyl)-acrylonitriles catalyzed by Cinchona ammonium salts.

Cyclopropane esters holding two quaternary centres were prepared in high yields, complete diastereoselection and up to 83% ee. The reaction described herein entailed reacting (Z)-3-substituted-2-(4-pyridyl)-acrylonitrile, a reactive class of Michael acceptor, with 2-bromomalonate esters in the presence of Cinchona derived phase-transfer catalysts. The reaction allowed multi-gram preparation of the desired products.

Insights on chiral, backbone modified peptide nucleic acids: Properties and biological activity.

PNAs are emerging as useful synthetic devices targeting natural miRNAs. In particular 3 classes of structurally modified PNAs analogs are herein described, namely α, β and γ, which differ by their backbone modification. Their mode and binding affinity for natural nucleic acids and their use in medicinal chemistry as potential miRNA binders is discussed.

Catalytic asymmetric conjugate addition of isocyanoacetate to (Z)-3-substituted-2-(4-pyridyl)-acrylonitrile, a reactive class of Michael acceptor.

(Z)-3-Substituted-2-(4-pyridyl)-acrylonitriles, a reactive class of Michael acceptors obtained exclusively as a single (Z) isomer, reacted with un-substituted isocyanoacetate esters mediated by phase-transfer catalysis to give, after base promoted cyclisation, functionalized imines in up to 94% ee and as a single diastereoisomer.

Catalytic enantioselective addition of isocyanoacetate to 3-methyl-4-nitro-5-styrylisoxazoles under phase transfer catalysis conditions.

The reaction between 3-methyl-4-nitro-5-styrylisoxazoles and ethyl isocyanoacetate proceeded under phase transfer catalysis to give enantioenriched monoadducts in high enantiomeric excess (up to 99% ee). The resulting adducts were subsequently cyclised to give 2,3-dihydropyrroles and substituted pyrrolidines in identical high ees and as a single diastereoisomer.

Fragment-Based Discovery of a Dual pan-RET/VEGFR2 Kinase Inhibitor Optimized for Single-Agent Polypharmacology.

Oncogenic conversion of the RET (rearranged during transfection) tyrosine kinase is associated with several cancers. A fragment-based chemical screen led to the identification of a novel RET inhibitor, Pz-1. Modeling and kinetic analysis identified Pz-1 as a type II tyrosine kinase inhibitor that is able to bind the "DFG-out" conformation of the kinase.

An improved procedure to prepare 3-methyl-4-nitroalkylenethylisoxazoles and their reaction under catalytic enantioselective Michael addition with nitromethane.

Herein, we describe a short synthesis of 3-methyl-4-nitro-5-alkylethenyl isoxazoles and their reactivity as Michael acceptors. The title compounds reacted with nitromethane under phase-transfer catalysis to provide highly enantioenriched adducts (up to 93% ee) which were then converted to the corresponding γ-nitroacids.

Phase transfer catalyzed enantioselective cyclopropanation of 4-nitro-5-styrylisoxazoles.

Heavily substituted cyclopropane esters were prepared in high yields, complete diastereoselection and high (up to 96%) enantioselectivity. The reaction described herein entailed reacting 4-nitro-5-styrylisoxazoles, a class of cinnamate synthetic equivalent, with 2-bromomalonate esters under the catalysis of 5 mol% of a Cincona derived phase-transfer catalyst. The reaction allowed multi-gram preparation of desired products.

DNA-based strategies for blocking HMGB1 cytokine activity: design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes.

In this work we report the design and synthesis of kinked oligonucleotide duplexes as potential inhibitors of HMGB1, a cytokine which triggers a broad range of immunological effects. We found that the designed ligands can interact with HMGB1, as evidenced by circular dichroism spectroscopy, and are able to block some extracellular effects induced by the protein, such as cellular proliferation and migration, as we demonstrated by in vitro biological assays. After selecting the most stable and active kinked duplex, we synthesized the corresponding PNA/DNA chimeric duplex which resulted to be more resistant to enzymatic degradation, and showed a biological activity comparable to that of the natural duplex.

Synthesis of a l-lysine-based alternate alpha,epsilon-peptide: a novel linear polycation with nucleic acids-binding ability.

A novel nucleic acid compaction device based on a positively-charged alpha,epsilon-poly-l-lysine was realized for the first time. The polycationic peptide was obtained by assembling Fmoc and Boc orthogonally protected l-lysine monomers by solid phase synthesis. The route to the novel polycation is very fast and convenient because it allows for the obtainment of the desired product in few synthetic steps exclusively employing Fmoc chemistry.

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009.

This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes.

Preliminary studies on noncovalent hyperbranched polymers based on PNA and DNA building blocks.

In this work, we report thermodynamic, kinetic, and microrheological studies relative to the formation of PNA- and PNA/DNA-based noncovalent polymeric systems, useful tools for biotechnological and bioengineering applications. We realized two kinds of systems: a PNA-based system formed by a self-assembling PNA tridendron, and a PNA/DNA hybrid system formed by a PNA tridendron and a DNA linker. The formation of a three-dimensional polymeric network, by means of specific Watson-Crick base pairing, was investigated by a detailed UV and CD spectroscopic study.

A White Campion (Silene latifolia) floral expressed sequence tag (EST) library: annotation, EST-SSR characterization, transferability, and utility for comparative mapping.

Background: Expressed sequence tag (EST) databases represent a valuable resource for the identification of genes in organisms with uncharacterized genomes and for development of molecular markers. One class of markers derived from EST sequences are simple sequence repeat (SSR) markers, also known as EST-SSRs. These are useful in plant genetic and evolutionary studies because they are located in transcribed genes and a putative function can often be inferred from homology searches.