Use of nucleoside phosphorylases for the preparation of 5-modified pyrimidine ribonucleosides.

Enzymatic transglycosylation, a transfer of the carbohydrate moiety from one heterocyclic base to another, is catalyzed by nucleoside phosphorylases (NPs) and is being actively developed and applied for the synthesis of biologically important nucleosides. Here, we report an efficient one-step synthesis of 5-substitited pyrimidine ribonucleosides starting from 7-methylguanosine hydroiodide in the presence of nucleoside phosphorylases (NPs).

Synthesis of Poly(ADP-ribose) Monomer Containing 2'-O-α-D-Ribofuranosyl Adenosine.

In this article, the earlier reported procedure for the synthesis of 2'-O-ß-D-ribofuranosyl nucleosides was extended to the synthesis of 2'-O-α-D-ribofuranosyl adenosine, a monomeric unit of poly(ADP-ribose). It consists in condensation of a small excess of 1-O-acetyl-2,3,5-tri-O-benzoyl-α,ß-D-arabinofuranose activated with tin tetrachloride with 3',5'-O-tetra-isopropyldisiloxane-1,3-diyl-ribonucleosides in 1,2-dichloroethane. The following debenzoylation and silylation of arabinofuranosyl residue and inversion of configuration at C-2'' atom of arabinofuranosyl residue and final removal of silyl protective groups gave 2'-O-α-D-ribofuranosyl adenosine in overall 13% to 21% yield. © 2019 by John Wiley & Sons, Inc.

Novel group of tyrosyl-DNA-phosphodiesterase 1 inhibitors based on disaccharide nucleosides as drug prototypes for anti-cancer therapy.

A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors based on disaccharide nucleosides was identified. TDP1 plays an essential role in the resistance of cancer cells to currently used antitumour drugs based on Top1 inhibitors such as topotecan and irinotecan. The most effective inhibitors investigated in this study have IC50 values (half-maximal inhibitory concentration) in 0.4-18.5 µM range and demonstrate relatively low own cytotoxicity along with significant synergistic effect in combination with anti-cancer drug topotecan. Moreover, kinetic parameters of the enzymatic reaction and fluorescence anisotropy were measured using different types of DNA-biosensors to give a sufficient insight into the mechanism of inhibitor's action.

Disaccharide pyrimidine nucleosides and their derivatives: a novel group of cell-penetrating inhibitors of poly(ADP-ribose) polymerase 1.

Nearly 30 synthetic nucleosides were tested with human recombinant poly(ADP-ribose) polymerase 1 as potential inhibitors of this enzyme. The most active compounds were some disaccharide analogues of thymidine: 3'-O-ß-D-ribofuranosyl-5-iodo-dUrd (2d; IC50 = 45 µM), 3'-O-ß-D-ribofuranosyl-2'-deoxythymidine (2e; IC50 = 38 µM), and 3'-O-ß-D-ribofuranosyl-2'-deoxythymidine oxidized (4; IC50 = 25 µM). These compounds also reduced H2O2-induced synthesis of poly(ADP-ribose) in cultured human ovarian carcinoma (SKOV-3) cells in a dose-dependent manner. Furthermore, compounds 2d or 2e until a concentration of 1 mM did not affect growth of SKOV-3 cells, whereas dialdehyde compound 4, as well as thymidine, exhibited a significant cytotoxicity.

Movements of birds and avian influenza from Asia into Alaska.

Asian-origin avian influenza (AI) viruses are spread in part by migratory birds. In Alaska, diverse avian hosts from Asia and the Americas overlap in a region of intercontinental avifaunal mixing. This region is hypothesized to be a zone of Asia-to-America virus transfer because birds there can mingle in waters contaminated by wild-bird-origin AI viruses. Our 7 years of AI virus surveillance among waterfowl and shorebirds in this region (1998-2004; 8,254 samples) showed remarkably low infection rates (0.06%). Our findings suggest an Arctic effect on viral ecology, caused perhaps by low ecosystem productivity and low host densities relative to available water. Combined with a synthesis of avian diversity and abundance, intercontinental host movements, and genetic analyses, our results suggest that the risk and probably the frequency of intercontinental virus transfer in this region are relatively low.

Synthesis of 2'-O-beta-d-Ribofuranosylnucleosides.

A simple and efficient method for the preparation of 2-O-beta-D-ribofuranosylnucleosides, minor tRNA components, is described in this unit. The method consists of condensation of a small excess of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose activated with tin tetrachloride with N-protected 3,5-O-tetra-isopropyldisiloxane-1,3-diyl-ribonucleosides in 1,2-dichloroethane. Subsequent deprotection produces 2-O-beta-D-ribofuranosylnucleosides in an overall yield of 46% to 72%.