doi: 10.15389/agrobiology.2021.3.434eng

UDC: 577.113.7:577.323.3:547.96:57.044



Yu.V. Chesnokov

Agrophysical Research Institute, 14, Grazhdanskii prosp., St. Petersburg, 195220 Russia, e-mail (corresponding author ✉)

Chesnokov Yu.V.

Received February 19, 2021

Modern concepts of intermolecular interactions in the cell are incomplete without understanding how complexes are formed between nucleic acids and the main intracellular components — water and proteins, and what determines the spatial stabilization of such complexes. The same is true for intercalation — intracellular intermolecular interaction of planar structure substances capable of being introduced between adjacent pairs of nitrogenous bases into DNA and RNA molecules, which plays a special role in pharmacology and genetic mutagenesis. In addition, intercalation can have a strong effect on cellular metabolism, slowing down and in some cases stopping the growth of cells, which, under certain conditions, leads to both apoptosis and cancer, or vice versa, to the body's recovery from such diseases (M. Ashrafizadeh et al., 2020). This review is devoted to the consideration of molecular mechanisms and the biological role of these processes. It is known that the DNA double helix can interact with polypeptides through the formation of specific hydrogen bonds between Watson-Crick base pairs and amino acid side chains (C.N. Pace et al., 2004), through intercalation of aromatic amino acid side chains between base pairs, at which some specificity is also manifested (A. Bazzoli et al., 2017), and due to the direct binding of protein α-helices and β-layers in DNA grooves (E. Del Giudice et al., 2009). It is assumed that the latter type of interaction takes place, for example, in DNA complexes with the cro-repressor of gene expression and with a protein that activates catabolism, for which two models of the binding of a-helices with the left-sided and right-sided DNA double helix in the B-form have been proposed. It is indicated that if the structure of a nucleic acid molecule is known, then the size of the surface of DNA and RNA available for water molecules or other solvents can be calculated. In the case of DNA folding in solution into a double helix, its molecule becomes polar. With this kind of hydration, two hydration shells are formed around the DNA molecule. The first of them, consisting of ~ 20 water molecules per nucleotide, is impermeable to cations and does not resemble ice in its aggregate structure, while the second shell is indistinguishable from ordinary water. Differences in the structure of hydration shells shed light on the nature of the conformational transition between the В ® А forms, which occurs with a decrease in the hydration of the DNA molecule. The interaction of nucleic acids with molecules of medicinal and other planar substances is also described. At the same time, the review considers only intercalation complexes with drugs whose molecules have a planar structure or have planar functional groups. It has been demonstrated that the binding of such substances with a double helix proceeds in two stages: at the first stage, they are attached along the periphery of the helix, at the second, intercalation occurs, that is, the actual insertion of the intercalator in the planar plane between nucleotide pairs. This kind of intercalation is accompanied by unwinding and elongation of the nucleic acid helix, as well as an increase in its rigidity. In accordance with the principle of exclusion of the nearest binding sites, according to which it does not occur at each nearest neighbor along the axis of the DNA double helix due to spatial constraints, which are determined by the stereometry of nucleotides adjacent to intercalators, intercalator molecules fill only half of such places. In general, the interactions of nucleic acids with water molecules, proteins and intercalators described in the work indicate the biological significance of this kind of relationship, since, as is known, the stability and regularity of the processes of replication and expression of genes plays an important role in the genotype—environment interaction and the «implementation» of genetic information at the molecular level.

Keywords: nucleic acids, A-DNA, B-DNA, conformational transitions, water molecules, DNA hydration, proteins, ligands, planar intercalators, intermolecular interactions, replication, gene expression.



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