The effect of chlorination of nucleotide bases on the conformational properties of thymidine monophosphate

Abstract

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 mono-I n a recent paper [1] it was reported that an international group of scientists working in xenobiology, a new brunch of life sciences, has succeeded in creating escherichia coli bacteria, in which DNA thymine was substituted with 5-chlorouracil of synthetic origin -a substance which is toxic to other organisms. Having successfully replaced the natural nucleotide base, the scientists began to test the vital functions of the modified organisms. They observed that such substitution did not affect the normal vital functioning of the bacteria and its ability to divide normally, but it was found that these investigated organisms were not capable to transfer the modified fragments of DNA to the bacteria with natural DNA (containing thymine), in other words they cannot change the normal organisms' genomes. Moreover, these mutated bacteria could not live even for one day without "toxic" environment, because 5-chlorouracil which is vital for them is not found in vivo. It was also revealed that even in environments where 5-chlorouracil is available in sufficient quantities, the lifetime of the new bacteria is several times lower than for similar bacteria with natural DNA.A reason for the reduced viability of bacteria with modified DNA can be modification of the AT pair donor-acceptor code in the DNA structure caused by the replacement of the methyl group of thymine with a chlorine atom. However, there is another possible mechanism for the effect of chlorination: changes in the conformational properties of nucleotides.Thus, the objective of our study is to find out what kind of changes in conformational and elastic properties of the monomers of this bacteria have been caused by the substitution of thymine with 5-chlorouracil. In addition to the potential usefulness to explain the peculiarities of life of the bacteria with modified DNA, solution of this problem has independent significance, because it allows tracing the relationship of the chemical structure and physical properties of biomolecules. materials and methodsAccording to the main task of the work a detailed quantum-mechanical conformational analysis of molecules of 5′-thymidylic acid (5TA)