[Chemical reactions catalyzed by DNA polymerases]. / Khimicheskie reaktsii, kataliziruemye DNK-polimerazami.

Chemical reactions catalyzed by various DNA polymerases are discussed, including DNA chain extension, the 3'-->5'-exonuclease proofreading activity, and some other pathways of replicative repair. The contribution of DNA polymerases to the fidelity of the template-dependent synthesis is analyzed by the examples of some most typical DNA polymerases.

[The successes and problems in the treatment of HIV infection: a biochemist's view]. / Uspekhi i problemy v lechenii VICh-infektsii: vzgliad biokhimika.

The problems of the effectiveness of the treatment of HIV-infected patients with 11 medicinal preparations and their combinations are discussed. 5 preparations (AZT, zalcitabine, videx, stavudine and lamivudine) are the nucleoside inhibitors of the synthesis of provirus DNA, catalyzed by inverse transcriptases; 2 preparations (nevirapine and rescriptor) are the inhibitors of this enzyme, having nonnucleoside nature, and 4 preparations (saquinarin, ritonavir, indinavir and nelfinavir) are the inhibitors of the processing of virus RNA, catalyzed by HIV protease. The modern concepts of the mechanism of action of the above-mentioned preparations are presented and the problem of the search of new effective medicinal preparations is discussed.

[Phosphorylation of 5'-O-phosphonylmethylthymidine and its incorporation into HeLa cells DNA]. / Fosforilirovanie 5'-O-fosfonilmetiltimidina i ego vkliuchenie v DNK kletok HeLa.

[3H]5'-O-Phosphonylmethylthymidine with a specific activity of 71 Ci/mmol was obtained by isotope exchange. Its incubation with a HeLa cell culture resulted in the formation of [3H]-labeled 5'-O-(beta-phosphoryl-alpha-phosphonylmethyl)thymidine, 5'-O-(beta,gamma-diphosphoryl-alpha-phosphonylmethyl)thymidine, and [3H]DNA. This proved the ability of 5'-O-phosphonylmethylthymidine to undergo phosphorylation and incorporation into the DNA of human cells.

[Azidothymidine, blocking telomerase functioning, shortens telomeric repeats in transformed human cells]. / Azidotimidin, blokiruia funktsiiu telomerazy, umen'shaet dlinu telomernykh povtorov v transformirovannykh kletkakh cheloveka.

The long-term action of azidothymidine, reverse transcriptase inhibitor, on cultivated U-937 (human promyelocyte leukemia) and MeWo (human melanoma) cells led to the concentration-dependent decrease in the length of telomeric chromosomal repeats. Telomere shortening was accompanied by temporary retardation of cell proliferation. Combined with the data obtained previously, these results suggest that azidothymidine inhibits telomerase functioning in cultivated cells.

[New nucleotide inhibitors of human DNA polymerase alpha]. / Novye nukleotidnye ingibitory DNK-polimerazy alpha cheloveka.

2'-Deoxythymidine 5'-triphosphate and 2'-deoxyadenosine 5'-triphosphate analogs containing a methylene group between the alpha phosphorus and 5' oxygen were synthesized. The substrate properties of these compounds toward some mammalian DNA polymerases and retroviral reverse transcriptases were evaluated using a system containing phage M13mp10 DNA, a synthetic oligonucleotide, and the enzyme. The compounds containing a hydroxyl at the 3' position were incorporated into the DNA chain by DNA polymerase alpha and terminal deoxynucleotidyl transferase, but were not recognized by retroviral reverse transcriptases and mammalian DNA polymerases epsilon and beta. The selectivity of the compounds synthesized was capitalized on during simultaneous isolation of DNA polymerases alpha and epsilon from human placenta. A methylene group was also introduced into the acyclovir molecule. It was shown that this modification inactivates furanose-related nucleotide analogs, but has a minor effect on the substrate properties of acyclic nucleotide analogs.

[Reactions of 5'-H-phosphonates, 5'-F-phosphates, and 5'-phosphates of modified thymidines in human blood plasma]. / Reaktsii 5'-H-fosfonataov, 5'-F-fosfatov i 5'-fosfatov modifitsirovannykh timidinov v plazme krovi cheloveka.

Mechanisms and rates of hydrolytic dephosphorylation of 5'-hydrogen phosphonates, 5'-fluorophosphates, and 5'-phosphates of 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, and thymidine in human blood serum were investigated. 5'-Hydrogen phosphonates of 3'-substituted thymidines are dephosphorylated 50-100 times slower than the corresponding 5'-phosphates. 5'-fluorophosphates of 3'-substituted thymidines are dephosphorylated 2 times slower than corresponding 5'-phosphates; first, substituted thymidine 5'-phosphates are formed, which are later dephosphorylated into substituted thymidines. These data illustrate probable molecular mechanisms of anti-HIV action of such nucleotides. 5'-hydrogen phosphonates of thymidines can serve as depot forms of corresponding thymidines, but other metabolic pathways are not excluded. Thymidine 5'-fluorophosphates can serve as depot-forms of both thymidines and their phosphates. Their fate in cells depends probably on their diffusion and on the activities of dephosphorylating and phosphorylating enzymes.