Synchronization transitions in a system of superdiffusively coupled neurons: Interplay of chimeras, solitary states, and phase waves.

In this paper, a network of interacting neurons based on a two-component system of reaction-superdiffusion equations with fractional Laplace operator responsible for the coupling configuration and nonlinear functions of the Hindmarsh-Rose model is considered. The process of synchronization transition in the space of the fractional Laplace operator exponents is studied. This parametric space contains information about both the local interaction strength and the asymptotics of the long-range couplings for both components of the system under consideration.

Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using Purine Nucleoside Phosphorylase.

1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task.

Chimera states in a chain of superdiffusively coupled neurons.

Two- and three-component systems of superdiffusion equations describing the dynamics of action potential propagation in a chain of non-locally interacting neurons with Hindmarsh-Rose nonlinear functions have been considered. Non-local couplings based on the fractional Laplace operator describing superdiffusion kinetics are found to support chimeras. In turn, the system with local couplings, based on the classical Laplace operator, shows synchronous behavior.

Intramolecular Hydrogen Bonding in N-Substituted 2-Chloroadenosines: Evidence from NMR Spectroscopy.

Two forms were found in the NMR spectra of N-substituted 2-chloroadenosines. The proportion of the mini-form was 11-32% of the main form. It was characterized by a separate set of signals in COSY, N-HMBC and other NMR spectra.

Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro.

A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of adenosine deaminase.

Design and Synthesis of New Modified Flexible Purine Bases as Potential Inhibitors of Human PNP.

The great interest in studying the structure of human purine nucleoside phosphorylase (PNP) and the continued search for effective inhibitors is due to the importance of the enzyme as a target in the therapy of T-cell proliferative diseases. In addition, PNP inhibitors are used in organ transplant surgeries to provide immunodeficiency during and after the procedure. Previously, we showed that members of the well-known fleximer class of nucleosides are substrates of PNP.

Rational Mutagenesis in the Lid Domain of Ribokinase from Results in an Order of Magnitude Increase in Activity towards D-arabinose.

Development of efficient approaches for the production of medically important nucleosides is a highly relevant challenge for biotechnology. In particular, cascade synthesis of arabinosides would allow relatively easy production of various cytostatic and antiviral drugs. However, the biocatalyst necessary for this approach, ribokinase from (RK), has a very low activity towards D-arabinose, making the synthesis using the state-of-art native enzyme technologically unfeasible.

Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods.

1,4-Pyrazine-3-carboxamide-based antiviral compounds have been under intensive study for the last 20 years. One of these compounds, favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, T-705), is approved for use against the influenza infection in a number of countries. Now, favipiravir is being actively used against COVID-19.

[Neurocognitive functioning in young patients with chronic endogenous depression].

Objective: To identify the specific features of cognitive functioning in patients with youth chronic endogenous depressions (YCED).

Material And Methods: Fifty-one male patients with YCED (duration 36.5±12.

Synthesis of 2-chloropurine ribosides with chiral amino acid amides at C6 and their evaluation as A adenosine receptor agonists.

A series of purine ribonucleosides bearing chiral amino acid amides at the C6 position of 2-chloropurine was synthesized. Molecular docking of the synthesized analogs of 2-chloroadenosine by their affinity for A adenosine receptors (AARs) was conducted. The investigation of AAR stimulating activity of synthesized nucleosides was carried out in a model of an isolated mouse atrium.

Synthesis of New 5'-Norcarbocyclic Aza/Deaza Purine Fleximers - Noncompetitive Inhibitors of Purine Nucleoside Phosphorylase.

A new series of flexible 5'-norcarbocyclic aza/deaza-purine nucleoside analogs were synthesized from 6-oxybicyclo[3.1.0.

Novel fleximer pyrazole-containing adenosine analogues: chemical, enzymatic and highly efficient biotechnological synthesis.

Nucleoside analogues have long served as key chemotherapeutic drugs for the treatment of viral infections and cancers. Problems associated with the development of drug resistance have led to a search for the design of nucleosides capable of bypassing point mutations in the target enzyme's binding site. As a possible answer to this, the Seley-Radtke group developed a flexible nucleoside scaffold (fleximers), where the heterocyclic purine base is split into its two components, i.

Multi-Enzymatic Cascades in the Synthesis of Modified Nucleosides: Comparison of the Thermophilic and Mesophilic Pathways.

A comparative study of the possibilities of using ribokinase → phosphopentomutase → nucleoside phosphorylase cascades in the synthesis of modified nucleosides was carried out. Recombinant phosphopentomutase from HB27 was obtained for the first time: a strain producing a soluble form of the enzyme was created, and a method for its isolation and chromatographic purification was developed. It was shown that cascade syntheses of modified nucleosides can be carried out both by the mesophilic and thermophilic routes from D-pentoses: ribose, 2-deoxyribose, arabinose, xylose, and 2-deoxy-2-fluoroarabinose.

Radical Dehalogenation and Purine Nucleoside Phosphorylase : How Does an Admixture of 2',3'-Anhydroinosine Hinder 2-fluoro-cordycepin Synthesis.

During the preparative synthesis of 2-fluorocordycepin from 2-fluoroadenosine and 3'-deoxyinosine catalyzed by purine nucleoside phosphorylase, a slowdown of the reaction and decrease of yield down to 5% were encountered. An unknown nucleoside was found in the reaction mixture and its structure was established. This nucleoside is formed from the admixture of 2',3'-anhydroinosine, a byproduct in the preparation of 3-'deoxyinosine.

The comparative analysis of the properties and structures of purine nucleoside phosphorylases from thermophilic bacterium HB27.

Two recombinant purine nucleoside phosphorylases from thermophilic bacterium HB27 encoded by genes TT_C1070 (PNPI) and TT_C0194 (PNPII) were purified and characterized. The comparative analysis of their sequences, molecular weight, enzymes specificity and kinetics of the catalyzed reaction were realized. As a result, it was determined that the PNPI is specific to guanosine while the PNPII to adenosine.

Thermophilic phosphoribosyltransferases HB27 in nucleotide synthesis.

Phosphoribosyltransferases are the tools that allow the synthesis of nucleotide analogues using multi-enzymatic cascades. The recombinant adenine phosphoribosyltransferase (APRT) and hypoxanthine phosphoribosyltransferase (HPRT) from HB27 were expressed in strains and purified by chromatographic methods with yields of 10-13 mg per liter of culture. The activity dependence of APRT and HPRT on different factors was investigated along with the substrate specificity towards different heterocyclic bases.

Crystal structure of Escherichia coli purine nucleoside phosphorylase in complex with 7-deazahypoxanthine.

Purine nucleoside phosphorylases (EC 2.4.2.

A Cascade of Thermophilic Enzymes As an Approach to the Synthesis of Modified Nucleotides.

We propose a new approach for the synthesis of biologically important nucleotides which includes a multi-enzymatic cascade conversion of -pentoses into purine nucleotides. The approach exploits nucleic acid exchange enzymes from thermophilic microorganisms: ribokinase, phosphoribosylpyrophosphate synthetase, and adenine phosphoribosyltransferase. We cloned the ribokinase gene from .

Recognition of Artificial Nucleobases by E. coli Purine Nucleoside Phosphorylase versus its Ser90Ala Mutant in the Synthesis of Base-Modified Nucleosides.

A wide range of natural purine analogues was used as probe to assess the mechanism of recognition by the wild-type (WT) E. coli purine nucleoside phosphorylase (PNP) versus its Ser90Ala mutant. The results were analyzed from viewpoint of the role of the Ser90 residue and the structural features of the bases.

The chemoenzymatic synthesis of clofarabine and related 2'-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases.

Two approaches to the synthesis of 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine (1, clofarabine) were studied. The first approach consists in the chemical synthesis of 2-deoxy-2-fluoro-α-D-arabinofuranose-1-phosphate (12a, (2F)Ara-1P) via three step conversion of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose (9) into the phosphate 12a without isolation of intermediary products. Condensation of 12a with 2-chloroadenine catalyzed by the recombinant E.

Possibility of usage of aminostigmine structural analogue for the treatment of toxic cognitive disorders.

We studied the effects of 2-(hexyl(methyl)amino)methyl)pyridyl-3-dimethyl carbamate (OPDC), a structural analogue of aminostigmine oxalate, on memory formation in rats with toxic scopolamine-induced amnesia. It was shown that OPDC in non-toxic doses ((1)/215 LD50) has significant anti-amnesic action. Ipidacrine and galantamine in the doses similar to toxic doses ((1)/17 and (1)/6 of LD50, respectively) induced the retention of memory trace.

3'-Azidothymidine in the active site of Escherichia coli thymidine phosphorylase: the peculiarity of the binding on the basis of X-ray study.

The structural study of complexes of thymidine phosphorylase (TP) with nucleoside analogues which inhibit its activity is of special interest because many of these compounds are used as chemotherapeutic agents. Determination of kinetic parameters showed that 3'-azido-3'-deoxythymidine (3'-azidothymidine; AZT), which is widely used for the treatment of human immunodeficiency virus, is a reversible noncompetitive inhibitor of Escherichia coli thymidine phosphorylase (TP). The three-dimensional structure of E.

[Study of tolerance of central muscarinic receptor blockers].

The tolerance of five central muscarinic receptor antagonists has been studied in experimental animals. According to the effect on orientation-exploratory reaction, drugs were arranged in the following order of increasing toxicity: procyclidine < trihexiphenidyl < benactizine < atropine < scopolamine. For the same therapeutic index, trihexiphenidyl and benactizine were characterized by the maximum tolerance (TD50/ED50 > 10) in mice.

[The arsenolysis reaction in the biotechnological method of synthesis of the ribavirin. Inhibition of reproduction of influenza A virus with the combination of ribavirin and ozeltamivir in experiments in vitro and in vivo].

Improved biotechnological method of receiving the antiviral drug ribavirin by the reaction of transglycosilation by addition of catalytic amounts of sodium arsenate in the reaction mixture. Such approach allows to hydrolyze the amount of the excess natural nucleoside donor--ribose and, as a consequence, to simplify the composition of the reaction mixture and the process of separation of ribavirin. The effect of ribavirin and ozeltamivir carboxylate and their combination on the reproduction of the virus of the influenza A in cell culture and in experiments on laboratory animals (mouse Balb/C).