Evidence map›Paper›PMID 21727088›Full record

ArticleNucleic acids research2011

Broad-spectrum aptamer inhibitors of HIV reverse transcriptase closely mimic natural substrates.

Mark A Ditzler, Debojit Bose, Nikolozi Shkriabai, Bruno Marchand, Stefan G Sarafianos, Mamuka Kvaratskhelia, Donald H Burke

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Betanodavirus and VER Disease: A 30-year Research Review.Pathogens (Basel, Switzerland) · 2020
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Aptamers against pathogenic microorganisms.Critical reviews in microbiology · 2016
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Aptamers: multifunctional molecules for biomedical research.Journal of molecular medicine (Berlin, Germany) · 2013
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Mark A DitzlerMolecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
Debojit Bose
Nikolozi Shkriabai
Bruno Marchand
Stefan G Sarafianos
Mamuka Kvaratskhelia
Donald H Burke
University of Missouri · US

Funding

Gene Therapy for HIV Using Aptamers that Target Reverse TranscriptaseR01AI074389 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI BURKE, DONALD H · 2008 to 2017
$4.5M
HIV-1 Integrase Structure and Function as a Therapeutic TargetK02AI077341 · NIAID · OHIO STATE UNIVERSITY · PI KVARATSKHELIA, MAMUKA · 2008 to 2012
$593k
NIAID NIH HHS 5R01AI074389NIAID NIH HHS AI062520NIAID NIH HHS AI077341
6 · The paper itself

Abstract

A detailed understanding of how aptamers recognize biological binding partners is of considerable importance in the development of oligonucleotide therapeutics. For antiviral nucleic acid aptamers, current models predict a correlation between broad-spectrum inhibition of viral proteins and suppression of emerging viral resistance, but there is little understanding of how aptamer structures contribute to recognition specificity. We previously established that two independent single-stranded DNA aptamers, R1T and RT1t49(-5), are potent inhibitors of reverse transcriptases (RTs) from diverse branches of the primate lentiviral family, including HIV-1, HIV-2 and SIV(cpz). In contrast, class 1 RNA pseudoknots, such as aptamer T1.1, are specific for RTs from only a few viral clades. Here, we map the binding interfaces of complexes formed between RT and aptamers R1T, RT1t49(-5) and T1.1, using mass spectrometry-based protein footprinting of RT and hydroxyl radical footprinting of the aptamers. These complementary methods reveal that the broad-spectrum aptamers make contacts throughout the primer-template binding cleft of RT. The double-stranded stems of these aptamers closely mimic natural substrates near the RNase H domain, while their binding within the polymerase domain significantly differs from RT substrates. These results inform our perspective on how sustained, broad-spectrum inhibition of RT can be achieved by aptamers.

Indexed as

Anti-HIV AgentsAptamers, NucleotideBinding SitesHIV Reverse TranscriptaseHydroxyl RadicalMass SpectrometryModels, MolecularProtein FootprintingProtein Structure, TertiaryReverse Transcriptase InhibitorsAnti-HIV AgentsAptamers, NucleotideHIV Reverse TranscriptaseHydroxyl Radicalreverse transcriptase, Human immunodeficiency virus 1Reverse Transcriptase Inhibitors

Identifiers

PMID21727088
PMCPMC3185408
OpenAlexW2104270477

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.