ArticleJournal of enzyme inhibition and medicinal chemistry2018
Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition.
Article in Journal of enzyme inhibition and medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- The Biological Impact of Some Phosphonic and Phosphinic Acid Derivatives on Human Osteosarcoma.Current issues in molecular biology · 2024Article
- Superanionic DNA: enzymatic synthesis of hypermodified DNA bearing four different anionic substituents at all four nucleobases.Nucleic acids research · 2023Article
- The altered metabolites contributed by dysbiosis of gut microbiota are associated with microbial translocation and immune activation during HIV infection.Frontiers in immunology · 2022Article
- N4-acyl-2'-deoxycytidine-5'-triphosphates for the enzymatic synthesis of modified DNA.Nucleic acids research · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors.
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Registered trials
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