THE EFFECT OF CHLORINATION OF NUCLEOTIDE BASES ON THE CONFORMATIONAL PROPERTIES OF THYMIDINE MONOPHOSPHATE.

Recent studies on Escherichia coli bacteria cultivation, in which DNA thymine was replaced with 5-chlorouracil have refreshed the problem of understanding the changes to physical properties of DNA monomers resultant from chemical modifications. These studies have shown that the replacement did not affect the normal activities and division of the bacteria, but has significantly reduced its life span. In this paper a comparative analysis was carried out by the methods of computational experiment of a set of 687 possible conformers of natural monomeric DNA unit (2'-deoxyribonucleotide thymidine monophosphate) and 660 conformers of 5-chloro-2'-deoxyuridine monophosphate - a similar molecules in which the natural nitrogenous base thymine is substituted with 5-chlorouracil. Structures of stable conformers of the modified deoxyribonucleotide have been obtained and physical factors, which determine their variation from the conformers of the unmodified molecule have been analyzed. A comparative analysis of the elastic properties of conformers of investigated molecules and non-covalent interactions present in them was conducted. The results can be usedfor planning experiments on synthesis of artficial DNA suitable for incorporation into living organisms.

How flexible are DNA constituents? The quantum-mechanical study.

Relaxed force constants (RFCs) and vibrational root-mean-square deviations have been evaluated by the original calculation method for conformational parameters of the DNA structural units and their constituents: nucleic acid bases (uracile, thymine, cytosine, adenine and guanine) and their 'building blocks' (benzene, pyrimidine, imidazole and purine molecules), as well as the DNA backbone structural units: tetrahydrofuran, 1,2-dideoxyribose, methanol and orthophosphoric acid. It has been found that the RFCs for nomenclature torsions beta, gamma, epsilon; and sugar pseudorotation angle P in 1,2-dideoxyribose are sensible to the molecule conformation and their values are in the range of 1-25 kcal/(mole·rad²) obeying the inequality K(γ)> K(ε) > K(ρ) > K(ß). The RFCs values for endocyclic torsions of nucleic acid bases six-member rings lie within 15-45 kcal/(mole·rad²) in pyrimidines and within 20-60 kcal/(mole·rad²) in purines. It is shown that the quantum zero-point motion effectively neglects the amino group non-planarity in cytosine, adenine and partially in guanine.