DNA and RNA polymerase substrates (dNTPs/NTPs)

DNA and RNA polymerase substrates, primarily deoxynucleoside triphosphates (dNTPs) and nucleoside triphosphates (NTPs), are the essential chemical precursors for the synthesis of DNA and RNA (Alberts et al., 2002). These molecules are recognized and processed by polymerase enzymes, which catalyze the formation of phosphodiester bonds to extend nucleic acid chains during replication and transcription (Jordan et al., 2020). In therapeutic development, this category is critical because it serves as the template for nucleoside and nucleotide analogs, a major class of drugs used in antiviral and anticancer therapy (Galmarini et al., 2001). These pharmacological analogs act as antimetabolites that compete with natural substrates for incorporation into viral or cellular genomes, often resulting in chain termination or the accumulation of deleterious mutations (Pruijssers & Denison, 2019). While highly effective, these agents can pose safety risks such as mitochondrial toxicity and myelosuppression due to off-target inhibition of host polymerases (Lewis et al., 2003).

Other names

Deoxynucleoside triphosphatesNucleoside triphosphatesNucleotide building blocksPolymerase precursors

Competitive inhibition of DNA or RNA polymerases and induction of premature chain termination or lethal mutagenesis (Galmarini et al., 2001; Pruijssers & Denison, 2019).