[Isosteric triphosphonate analogues of dNTP: synthesis and substrate properties toward various DNA polymerases].

Isosteric triphosphonate derivatives of 2',3'-dideoxy-2',3'-didehydroadenosine and 3'-deoxy-2',3'-didehydrothymidine and their beta,gamma-substituted analogues were synthesized. Their substrate properties toward a number of reverse transcriptases of the human immunodeficiency and bird myeloblastosis viruses, human DNA polymerases alpha and beta, and the Klenow fragment of Escherichia coli DNA polymerase I were studied.

[Efficiency of anti-inflammatory therapy for experimental tuberculosis in genetically tuberculosis-sensitive mice].

The study assessed trends in death rates in genetically tuberculosis-sensitive I/St mice, mycobacterial seeding from their organs, and the magnitude of abnormal changes in the lung after intratracheal Mycobacterium tuberculosis infection of recipients. The experimental animals received two anti-inflammatory regimens: 1) a very small-dose intravenous injection of immature antigen-loaded bone marrow-derived syngeneic dendritic cells; 2) the nonsteroidal anti-inflammatory drug diclofenac injected intramuscularly in the course of disease development. Both anti-inflammatory regimens caused a significant increase in the animals' survival, a reduction in the amount of mycobacteria in the lung and the pulmonary infiltration with lymphoid cells as compared with untreated infected control animals. These findings indicate that suppression of an excessive inflammatory process in the lung may have a beneficial antituberculous effect in tuberculosis-sensitive animals.

[Nucleotide-dependent degradation of nucleic acids by DNA and RNA polymerases]. / Nukeleotid-zavisimaia degradatsiia nukleinovykh kislot DNK- i RNK-polimerazami.

In this review we summarize the current knowledge about recently discovered reactions of nucleotide-dependent nucleic acid degradation catalyzed by DNA and RNA polymerases. These reactions consist in the excision of the 3'-nucleotide of nascent DNA or RNA chain in the presence of non-complementary r/dNTPs. In the case of DNA polymerases the dinucleoside-5',5"-tetraphosphate as a product of the reaction is formed. In contrast, in the case of RNA polymerases non-complementary r/dNTPs stimulate 3'-->5' exonuclease degradation of RNA transcript. The possible role of these reactions in fidelity of DNA and RNA synthesis, in resistance of HIV reverse transcriptase towards nucleoside inhibitors is discussed.

Stereochemical control of DNA biosynthesis.

Stereochemical control of DNA biosynthesis was studied using several DNA-synthesizing complexes containing, in each case, a single substitution of a 2'-deoxy-D-nucleotide residue by an enantiomeric L-nucleotide residue in a DNA chain (either in the primer or in the template) as well as 2'-deoxy-L-ribonucleoside 5'-triphosphates (L-dNTPs) as substrates. Three template-dependent DNA polymerases were tested, Escherichia coli DNA polymerase I Klenow fragment, Thermus aquaticus DNA polymerase and avian myeloblastosis virus reverse transcriptase, as well as template-independent calf-thymus terminal deoxynucleotidyl transferase. Very stringent control of stereoselectivity was demonstrated for template-dependent DNA polymerases, whereas terminal deoxynucleotidyl transferase was less selective. DNA polymerase I and reverse transcriptase catalyzed formation of dinucleoside 5',5'-tetraphosphates when L-dTTP was used as substrate. Comparison between models of template-primer complexes, modified or not by a single L-nucleotide residue, revealed striking differences in their geometry.