ArticleNucleic acids research2007
Active site binding and sequence requirements for inhibition of HIV-1 reverse transcriptase by the RT1 family of single-stranded DNA aptamers.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Biophysical Characterization of Novel DNA Aptamers against K103N/Y181C Double Mutant HIV-1 Reverse Transcriptase.Molecules (Basel, Switzerland) · 2022Article
- Aptamers for Anti-Viral Therapeutics and Diagnostics.International journal of molecular sciences · 2021Review
- Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase.Nucleic acids research · 2020Article
- Predicting Future Prospects of Aptamers in Field-Effect Transistor Biosensors.Molecules (Basel, Switzerland) · 2020Article
- Poly-Target Selection Identifies Broad-Spectrum RNA Aptamers.Molecular therapy. Nucleic acids · 2018Article
- Aptamers against pathogenic microorganisms.Critical reviews in microbiology · 2016Review
- Structure of HIV-1 reverse transcriptase bound to a novel 38-mer hairpin template-primer DNA aptamer.Protein science : a publication of the Protein Society · 2016Article
- Potent Inhibition of HIV-1 Reverse Transcriptase and Replication by Nonpseudoknot, "UCAA-motif" RNA Aptamers.Molecular therapy. Nucleic acids · 2013Article
- High-throughput sequence analysis reveals structural diversity and improved potency among RNA inhibitors of HIV reverse transcriptase.Nucleic acids research · 2013Article
- Novel cell and gene therapies for HIV.Cold Spring Harbor perspectives in medicine · 2012Review
- DNA aptamers to human immunodeficiency virus reverse transcriptase selected by a primer-free SELEX method: characterization and comparison with other aptamers.Nucleic acid therapeutics · 2012Article
- Broad-spectrum aptamer inhibitors of HIV reverse transcriptase closely mimic natural substrates.Nucleic acids research · 2011Article
- Novel bimodular DNA aptamers with guanosine quadruplexes inhibit phylogenetically diverse HIV-1 reverse transcriptases.Nucleic acids research · 2008Article
- Novel aptamer inhibitors of human immunodeficiency virus reverse transcriptase.Oligonucleotides · 2008Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Nucleic acid aptamers can potentially be developed as broad-spectrum antiviral agents. Single-stranded DNA (ssDNA) aptamer RT1t49 inhibits reverse transcriptases (RT) from HIV-1 and diverse lentiviral subtypes with low nanomolar values of Kd and IC50. To dissect the structural requirements for inhibition, RT-catalyzed DNA polymerization was measured in the presence of RT1t49 variants. Three structural domains were found to be essential for RT inhibition by RT1t49: a 5' stem (stem I), a connector and a 3' stem (stem II) capable of forming multiple secondary structures. Stem I tolerates considerable sequence plasticity, suggesting that it is recognized by RT more by structure than by sequence-specific contacts. Truncating five nucleotides from the 3' end prevents formation of the most stable stem II structure, yet has little effect on IC50 across diverse HIV-1, HIV-2 and SIV(CPZ) RT. When bound to wild-type RT or an RNase H active site mutant, site-specifically generated hydroxyl radicals cleave after nucleotide A32. Cleavage is eliminated by either of two polymerase (pol)-active site mutants, strongly suggesting that A32 lies within the RT pol-active site. These data suggest a model of ssDNA aptamer-RT interactions and provide an improved molecular understanding of a potent, broad-spectrum ssDNA aptamer.
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