Derivatives of 3-Deoxy-3-(N-Hydroxyamino)-D-Ribose

Abstract

A series of 3-(N-arylmethyl-N-hydroxyamino)-l,2-O-cyclopentylidene-3-deoxy-5-O-toluoyl-α-D-riboses has been prepared. The blocking groups used were chosen to allow an easy nucleosidation of these compounds to spin labelled analogs of natural nucleosides. The conformational behavior of the N-arylmethyl-N-hydroxyamino group has been studied using ³/_CH NMR coupling data and molecular mechanics computations. Upon spontaneous oxidation, these hydroxylamines led to the corresponding aminoxyl free radicals which were submitted to EPR spectroscopy and quantum mechanical computations at a semiempirical level (PM3).     

Minimum Evaporation Model of Dermatological Delivery Systems. Lamellar Liquid Crystal Formulations Containing Brazilian Nut (Bertholletia excelsa HBK) Vegetable Oil and Guarana Glycolic Extract

Formulations with lyotropic liquid crystals were prepared from a Brazilian nut vegetable oil, guarana extract and combination of sorbitan monooleate (Span 80) and sorbitan monolaurate ethoxylate EO 20 (Tween 20) in the ratio 1:3 (surfactant component) and their physical–chemical aspects and rheological properties were determined. Compositions with liquid crystals were found in the pseudoternary diagram in a surfactant range of 70–90% and polarized light microscopy, small-angle x-ray scattering (SAXS) showed them to be lamellar. The preparations were furthermore characterized rheologically by shear stress shear rate sweeps finding plastic and pseudoplastic behavior without thixotropy. Electric conductivity and pH measurements demonstrated a potential for future application as dermatological delivery system of the active compounds in the Bertholletia excelsa and Paullinia cupana.      

Optical constants of organic insulators in the UV range extracted from reflection electron energy loss spectra

Reflection electron energy loss spectroscopy (REELS) spectra were measured for seven insulating organic compounds (DNA, Irganox 1010, Kapton, polyethylene [PE], poly(methyl methacrylate) [PMMA], polystyrene [PS] and polytetrafluoroethylene [PTFE]). Optical constants and energy band gaps were extracted from the measured REELS spectra after elimination of multiple electron scattering via a deconvolution and fitting the normalised single scattering energy loss spectra to Drude and Drude–Lindhard model dielectric functions, constrained by the Kramers–Kronig sum and f-sum rules. Satisfactory agreement is found for those optical constants for which literature data exists. For PTFE, the observed features in the optical data correspond to its electronic structure.     

Photoactivatable V-Shaped Bifunctional Quinone Methide Precursors as a New Class of Selective G-quadruplex Alkylating Agents

Combining the selectivity of G-quadruplex (G4) ligands with the spatial and temporal control of photochemistry is an emerging strategy to elucidate the biological relevance of these structures. In this work, we developed six novel V-shaped G4 ligands that can, upon irradiation, form stable covalent adducts with G4 structures via the reactive intermediate, quinone methide (QM). We thoroughly investigated the photochemical properties of the ligands and their ability to generate QMs. Subsequently, we analyzed their specificity for various topologies of G4 and discovered a preferential binding towards the human telomeric sequence. Finally, we tested the ligand ability to act as photochemical alkylating agents, identifying the covalent adducts with G4 structures. This work introduces a novel molecular tool in the chemical biology toolkit for G4s.     

Chiral Fibers Formation Upon Assembly of Tetraphenylalanine Peptide Conjugated to a PNA Dimer

Self-assembly of biomolecules such as peptides, nucleic acids or their analogues affords supramolecular objects, exhibiting structures and physical properties dependent on the amino-acid or nucleobase composition. Conjugation of the peptide diphenylalanine (FF) to peptide nucleic acids triggers formation of self-assembled structures, mainly stabilized by interactions between FF. In this work we report formation of homogeneous chiral fibers upon self-assembly of the hybrid composed of the tetraphenylalanine peptide (4F) conjugated to the PNA dimer adenine-thymine (at). In this case nucleobases seem to play a key role in determining the morphology and chirality of the fibers. When the PNA “at” is replaced by guanine-cytosine dimer “gc”, disordered structures are observed. Spectroscopic characterization of the self-assembled hybrids, along with AFM and SEM studies is reported. Finally, a structural model consistent with the experimental evidence has also been obtained, showing how the building blocks of 4Fat arrange to give helical fibers.     

Zn-Induced Interactions Between SARS-CoV-2 orf7a and BST2/Tetherin

We present in this work a first X-ray Absorption Spectroscopy study of the interactions of Zn with human BST2/tetherin and SARS-CoV-2 orf7a proteins as well as with some of their complexes. The analysis of the XANES region of the measured spectra shows that Zn binds to BST2, as well as to orf7a, thus resulting in the formation of BST2-orf7a complexes. This structural information confirms the the conjecture, recently put forward by some of the present Authors, according to which the accessory orf7a (and possibly also orf8) viral protein are capable of interfering with the BST2 antiviral activity. Our explanation for this behavior is that, when BST2 gets in contact with Zn bound to the orf7a Cys₁₅ ligand, it has the ability of displacing the metal owing to the creation of a new disulfide bridge across the two proteins. The formation of this BST2-orf7a complex destabilizes BST2 dimerization, thus impairing the antiviral activity of the latter.     

Measuring local pH in electrochemistry

Localized pH measurements are important in various areas of electrochemistry, from corrosion to bio-electrochemistry and electrocatalysis. Different techniques are available to perform these measurements and offer numerous possibilities in terms of spatial and temporal resolution, sensitivity, and precision. In this brief review we present the recent progress made and summarize the main techniques available for localized pH measurements in electrochemistry such as scanning probe techniques (SECM, SICM, SIET), laser (confocal) fluorescence microscopy, rotating ring-disc electrode (RRDE) voltammetry, and infra-red spectroscopy, among others.     

In Vitro Effects of Sulforaphane on Interferon-Driven Inflammation and Exploratory Evaluation in Two Healthy Volunteers

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.     

Exploiting Protein N-Terminus for Site-Specific Bioconjugation

Although a plethora of chemistries have been developed to selectively decorate protein molecules, novel strategies continue to be reported with the final aim of improving selectivity and mildness of the reaction conditions, preserve protein integrity, and fulfill all the increasing requirements of the modern applications of protein conjugates. The targeting of the protein N-terminal alpha-amine group appears a convenient solution to the issue, emerging as a useful and unique reactive site universally present in each protein molecule. Herein, we provide an updated overview of the methodologies developed until today to afford the selective modification of proteins through the targeting of the N-terminal alpha-amine. Chemical and enzymatic strategies enabling the selective labeling of the protein N-terminal alpha-amine group are described.