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.

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.

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.

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.

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.

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

Purine nucleoside phosphorylases (EC 2.4.2.

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.