| Abstract [eng] |
Human immunodeficiency virus remains a serious threat for human health: over 36 million are infected with HIV, of which 1.8 million die each year. Retroviruses have a unique viral reproduction strategy employing reverse transcriptase for DNA biosynthesis from viral RNA. HIV 1 reverse transcriptase is among the most important targets for antiviral treatment. M. MuLV reverse transcriptase belongs to retroviral polymerases and, although structurally similar to HIV 1 reverse transcriptase, has distinct biochemical properties. These reverse transcriptases exhibit biochemical properties different from the host replication polymerase mode of action. The ability to utilize properties of polymerases would allow the development of inhibitors directed against viral polymerases without affecting of the host polymerases. In parallel, the ability of polymerases to use alternatively structured nucleotides would allow synthesizing DNA with additional functionalities. The use of modified nucleotides for DNA biosynthesis has become the subject of synthetic biology research in order to broaden the genetic code and create an artificial functional biological system with wider application possibilities. In this work, the use of modified pyridone nucleosides and nucleotides in DNA biosynthesis, as well as phosphonoacetic acid nucleotide conjugates designed to inhibit target DNA polymerases, are discussed. |
