Inhibitor DNA dan RNA Polymerase

DNA polymerases build DNA by forming a phosphodiester bond between the 5´α-phosphate of one deoxyribonucleotide and the 3´-hydroxyl of another. They cannot initiate DNA synthesis de novo, but add deoxynucleotides, one at a time, to the 3´-hydroxyl terminus of a preexisting DNA or RNA strand (a primer). Most DNA polymerases require a template bound to the primer, and extend the primers by synthesizing strands complementary to the template; while most prefer DNA templates, reverse transcriptase prefers RNA templates. Some DNA polymerases, such as terminal transferase, are templateindependent. RNA polymerases build (transcribe) RNA strands by forming a phosphodiester bond between the 5´α-phosphate of one ribonucleotide and the 3´-hydroxyl of another. DNA template-dependent RNA polymerases can initiate RNA strand synthesis de novo, yielding complementary RNA transcripts. Poly-A polymerase is template-independent, and adds A residues to the 3´-hydroxyl termini of preexisting RNA transcripts. Retroviruses specify reverse transcriptases, which are RNA-dependent DNA polymerases that reverse transcribe the retroviral RNA genome into DNA.

Inhibitors of DNA and RNA polymerases are invaluable tools in both clinical and research settings. The use of DNA and RNA polymerase inhibitors aids in delineating the mechanistic aspects of transcription and DNA replication, in defining structure-function relationships, and in protein turnover studies. Characterizing mutations that can confer resistance to antibiotics can help identify the genomic loci that encode for the respective subunit of the target enzyme. As DNA and RNA polymerases are among the most attractive drug targets, the knowledge about these inhibitors, their structures, and their modes of action provides the basis for design of new drugs/ antibiotics that will be effective against new pathogens and antibiotic-resistant mutants of known pathogens. Because some of these agents block specific steps (transcription) in the processes that lead from DNA to protein, their use can help delineate the role of transcriptional control in regulating the expression of target genes in health and disease. Furthermore, some of these inhibitors can be used in studies requiring the synchronization of the cell cycle; also since some have been reported to induce and/or inhibit apoptosis, these represent valuable tools for apoptosis-related studies.