Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity

Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]⁶-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them achieved enhanced AT₂R/AT₁R subtype selectivity. This diversification has been studied through 2D NMR spectroscopy and unveiled a putative more structured microenvironment for the two selective ligands accompanied with increased number of NOE cross-peaks. The most potent analogue, compound 2 , has been explored regarding its neurotrophic potential and resulted in an enhanced neurite growth with respect to the established agent C21.     

Enhanced stability of a Prussian blue/sol-gel composite for electrochemical determination of hydrogen peroxide

We have prepared a sol–gel that incorporates Prussian Blue (PB) as a redox mediator. It is shown that the PB in the pores of the sol–gel retains its electrochemical activity and is protected from degradation at acidic and neutral pH values. TEM and EDX studies revealed the PB nanoparticles to possess a cubic crystal structure and to be well entrapped and uniformly dispersed in the pores of the matrix. The electrocatalytic activity of the materials toward hydrogen peroxide (H₂O₂) was studied by cyclic voltammetry and amperometry. The modified electrode displays good sensitivity for the electrocatalytic reduction of H₂O₂ both in acidic (pH 1.4) and neutral media. The sensor has a dynamic range from 3 to 210 μM of H₂O₂, and the detection limit is 0.6 μM (at an SNR of 3).

Diorganotin(IV) compounds containing 2-(Et2NCH2)C6H4 moieties: Configurational stability in solution and solid state structures

Hypercoordinated diorganotin(IV) dichloride, [2-(Et₂NCH₂)C₆H₄]₂SnCl₂ (1), was prepared by reacting [2-(Et₂NCH₂)C₆H₄]Li with SnCl₄. Halide-exchange reactions between 1 and the appropriate potassium halides gave [2-(Et₂NCH₂)C₆H₄]₂SnX₂ [X = F (2), Br (3), I (4)]. Reaction of 1 with excess of Na₂S gave the cyclo-[{2-(Et₂NCH₂)C₆H₄}₂SnS]₂ (5). The solution behavior of the title compounds in solution was investigated by multinuclear (¹H, ¹³C, ¹⁹F and ¹¹⁹Sn) NMR spectroscopy, including variable temperature studies. Single-crystal X-ray diffraction analysis revealed for all compounds intramolecular N → Sn coordination thus resulting in distorted octahedral (C,N)₂SnX₂ configurations. Planar chirality is observed as result of the non-planarity of the SnC₃N rings; all compounds, however, crystallizing as racemates. The isomers are linked by extensive hydrogen bonds to give different supramolecular architectures in the crystals of compounds 1, 3 and 4.     

Geographic Variability of Berry Phytochemicals with Antioxidant and Antimicrobial Properties

The aim of this study was to determine the variability of several chemical compounds and the antioxidant and antimicrobial activities of eight types of berries harvested from two different geographical regions in the same year. The analyses were performed on bilberry, black currant, gooseberry, red currant, raspberry, sea buckthorn, strawberry and sour cherry, which were handpicked during the summer of 2019, in the same periods when they are typically harvested for consumer purposes. Total anthocyanins content (TAC), total flavonoids content (TFC), total polyphenolic compounds (TPC), determination of the Ferric-Reducing Antioxidant Power (FRAP), determination of the DPPH free radical scavenging assay (RSA), determination of nine phenolic compounds by HPLC-UV assay and antimicrobial activity were determined for undiluted hydroalcoholic extracts of all the studied berries. The results showed that the berries from Romania were richer in antioxidant compounds than the berries from Russia. The TPC content varied between 4.13–22.2 mg GAE/g d.w., TFC between 3.33–8.87 mg QE/g d.w. and TAC between 0.13–3.94 mg/g d.w. The highest variability was determined for TPC. Regarding the antioxidant activity assessed by FRAP assay, values were between 6.02–57.23 µmols TE/g d.w. and values for the RSA method between 18.44–83.81%. From the eight types of berries analyzed, bilberries and raspberries had the highest antioxidant activity considering both regions and both determination methods. Not only the type, but also the environmental and cultivation conditions in which the berries grow, can lead to variations in their chemical composition. The extracted polyphenolic compounds from the studied berries showed antibacterial properties on pathogens, such as Escherichia coli, Bacillus subtilis and Staphyloccocus aureus. The inhibitory action on Salmonella typhi and fungi Candida albicans and Aspegillus niger was absent to very low. The antimicrobial activity of the hydroalcoholic extracts was dependent on the provenance of the berries, too.     

Helical aquatubes of calix[4]arene di-methoxycarboxylic acid

Two trimeric units of calix[4]arene di-methoxycarboxylic acid form a six-pointed star architecture that, in turn, generates triple helical aquatubes which intermesh between themselves by aromatic-aromatic interdigitation of the macrocycle.     

Evaluation of Meldola Blue‐Carbon Nanotube‐Sol‐Gel Composite for Electrochemical NADH Sensors and Their Application for Lactate Dehydrogenase‐Based Biosensors

A novel MB‐SWNT‐sol‐gel nanocomposite material was prepared by the sol‐gel process incorporating a redox mediator and carbon nanotubes. The electrocatalytic properties of the nanomaterial based sensor toward NADH oxidation were studied by electrochemical measurements. Significant enhancement of oxidation current is obtained at electrodes modified by MB‐SWNT‐sol‐gel in comparison with the analogous carbon black and/or graphite composite modified electrode. The usefulness of the nanocomposite material as a matrix for immobilizing enzymes is also demonstrated. Analytical parameters of D ‐lactate biosensors with and without SWNT in the hybrid film were compared demonstrating that performance of the biosensor was significantly improved when introducing SWNT.     

PVA-DNA cryogel membranes: characterization, swelling, and transport studies

Double-stranded (ds) DNA from salmon testes has been incorporated into PVA hydrogels obtained by a technique of repeated freezing and thawing. The cryogels obtained are free of potential toxic species like chemical cross-linkers, and consequently, they can be used in pharmaceutical or medical applications. These cryogels show a good mechanical resistance and a white and opaque appearance caused by a heterogeneous porous structure. Encapsulated DNA molecules can be in a compacted or an extended conformation in the PVA matrix and can be controlled by tailoring the degree of crystallinity of the PVA network; this is supported by fluorescence microscopy and UV and FTIR spectroscopic studies. The two forms of encapsulated DNA were observed for different types of matrixes: an extended one in a more crystalline network and a globular one in a more amorphous one. Different associations of base pairs have also been observed. PVA cryogel crystallinity could be tailored by the cryogel contact with different salt solutions. Cryogel surface (scanning electron microscopy) and bulk morphology (porosimetry), swelling, DNA retention, and delivery kinetics have also been studied. All these investigations clearly show strong interactions between PVA and DNA.     

Parametrized riccati equations for controlled linear differential systems with jump Markov perturbations

An input-output linear time-varying differential system with homogeneous jump Markov parameters and mean square exponential stable evolution is considered. We define a family T(t), t ≥ 0 of linear bounded input-output operators. It is proved that if sup ‖T(t)‖<γ then a parametrized by γ differential Riccati type system has a unique global bounded and stablizing solution. An application to the estimate of a stability radius is given