ArticleOrganic & biomolecular chemistry2016
Exploring the role of the α-carboxyphosphonate moiety in the HIV-RT activity of α-carboxy nucleoside phosphonates.
Article in Organic & biomolecular chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies.International journal of molecular sciences · 2023Review
- Microwave-Accelerated McKenna Synthesis of Phosphonic Acids: An Investigation.Molecules (Basel, Switzerland) · 2023Article
- Synthesis and Evaluation of Prodrugs of α-Carboxy Nucleoside Phosphonates.The Journal of organic chemistry · 2022Article
- Sliding of HIV-1 reverse transcriptase over DNA creates a transient P pocket - targeting P-pocket by fragment screening.Nature communications · 2021Article
- Evolving understanding of HIV-1 reverse transcriptase structure, function, inhibition, and resistance.Current opinion in structural biology · 2020Review
- The McKenna reaction - avoiding side reactions in phosphonate deprotection.Beilstein journal of organic chemistry · 2020Article
- Structural Basis of HIV-1 Inhibition by Nucleotide-Competing Reverse Transcriptase Inhibitor INDOPY-1.Journal of medicinal chemistry · 2019Article
- Alpha-carboxynucleoside phosphonates: direct-acting inhibitors of viral DNA polymerases.Future medicinal chemistry · 2019Review
- On the Reaction of Carbonyl Diphosphonic Acid with Hydroxylamine and O-alkylhydroxylamines: Unexpected Degradation of P-C-P Bridge.Molecules (Basel, Switzerland) · 2017Article
- Through-bond effects in the ternary complexes of thrombin sandwiched by two DNA aptamers.Nucleic acids research · 2017Article
- Conformational States of HIV-1 Reverse Transcriptase for Nucleotide Incorporation vs Pyrophosphorolysis-Binding of Foscarnet.ACS chemical biology · 2016Article
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Authors and funding
7 authors.
Funding
Abstract
As α-carboxy nucleoside phosphonates (α-CNPs) have demonstrated a novel mode of action of HIV-1 reverse transcriptase inhibition, structurally related derivatives were synthesized, namely the malonate 2, the unsaturated and saturated bisphosphonates 3 and 4, respectively and the amide 5. These compounds were evaluated for inhibition of HIV-1 reverse transcriptase in cell-free assays. The importance of the α-carboxy phosphonoacetic acid moiety for achieving reverse transcriptase inhibition, without the need for prior phosphorylation, was confirmed. The malonate derivative 2 was less active by two orders of magnitude than the original α-CNPs, while displaying the same pattern of kinetic behavior; interestingly the activity resides in the “L”-enantiomer of 2, as seen with the earlier series of α-CNPs. A crystal structure with an RT/DNA complex at 2.95 Å resolution revealed the binding of the “L”-enantiomer of 2, at the polymerase active site with a weaker metal ion chelation environment compared to 1a (T-α-CNP) which may explain the lower inhibitory activity of 2.
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