Theoretical predictions of the impact of the trisubstituted pyrophosphate internucleotide bond on B DNA fragments

Transcription factor NF-κB has the ability to recognize and to bind the DNA sequence of various genes involved in numerous physiological processes, such as a regulation of immunoresponse, inflammation or cellular growth and development. Replacement of the phosphodiester fragment in the κB site by the trisubstituted pyrophosphate (TSP) residue can cause the DNA molecule to become an irreversible and specific inhibitor of NF-κB protein. It arises from the fact that the TSP residue has ability to create the covalent bond with ε-amino groups of lysine. The main purpose of this work was to investigate if the modifications of the sugar-phosphate backbone influences considerably the structure of the DNA molecule. Three models of the asymmetric DNA duplexes containing target sequences for NF-κB factor (5′-GGAAAGTCCC-3′) were a subject of the examinations of the structural changes. Two of them had incorporated TSP residue. The results show that the TSP group seems to not cause global changes in the structure of the native DNA fragment, however some local distortions occur but their magnitudes are small.