ß-Like DNA polymerases and prospects for their use as targets in chemotherapy of tumors.

DNA polymerases ß are enzymes that perform repair of damaged DNA. In the cells of malignant tumors, there is a change in the production and properties of these enzymes, which is accompanied by altered viability of tumor cells. Analysis of the publications available in Russian and international databases (Pubmed, Elsevier) on the structure and properties of DNA polymerases ß and their role in cell growth and proliferation, published over the past 20 years, has shown overexpression of genes encoding ß-like DNA polymerases in many types of malignant tumors cells. This explains the maintenance of their viability and proliferative activity. Targeted inhibition of ß-like DNA polymerases is accompanied by antiproliferative and antitumor effects. Stable paramagnetic isotopes of magnesium (25Mg2+) or other divalent metals (43Ca2+ and 67Zn2+) with uncompensated nuclear spin isotopes, as well as short single-stranded polydeoxyribonucleotides, can be used as promising antitumor pharmacophores.

Oligomerization of ß-Like DNA Polymerases in the Presence of Fe2+ Ions.

This work presents data on the relationship between the oligomeric state and catalytic activity of ß-like DNA polymerases isolated from three cancer cell lines upon replacement of magnesium ions with iron. It was shown that the suppression of the catalytic activity of ß-like DNA polymerases in the presence of divalent iron ions is related to enzyme oligomerization that can be responsible for the suppression of the magnetic isotope effect.

Radiation-Chemical Biotechnology for Producing Ultrashort (50-100n) Single-Chain Polydeoxyribonucleotides with Anticancer Activity.

The fundamental possibility of obtaining ultrashort (50n-100n) single-stranded polydeoxyribonucleotides by the method of radiation-chemical destruction of total yeast DNA was established and their anticancer activity was shown.

L, D-Polydeoxyribonucleotides to provide an essential inhibitory effect on DNA polymerase ß of human myeloid leukemia HL60 cells.

The inhibitory effect of D and L-polynucleotides of a given length (40-50n) on the catalytic activity of DNA polymerase ß isolated from chromatin cells of acute myeloid leukemia HL-60 was evaluated. The synthesized L enantiomer was found to have a higher inhibitory activity than the synthesized and isolated D enantiomers of polynucleotides. The work also proposes a biophysical model that describes this effect.