Evidence map›Paper›PMID 21280608›Full record

ArticleJournal of the American Chemical Society2011

Solution structure of a DNA duplex containing the potent anti-poxvirus agent cidofovir.

Olivier Julien, James R Beadle, Wendy C Magee, Subhrangsu Chatterjee, Karl Y Hostetler, David H Evans, Brian D Sykes

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 26 citations in OpenAlex.

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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 2 institutions in 2 countries.

Olivier JulienDepartment of Biochemistry, University of Alberta, 4-19 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
James R Beadle
Wendy C Magee
Subhrangsu Chatterjee
Karl Y Hostetler
David H Evans
Brian D Sykes
University of Alberta · CAUniversity of California, San Diego · US

Funding

Orally Active Nucleoside Phosphonates for Hepatitis C VirusR01AI076558 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHOOLEY, ROBERT TURNER · 2009 to 2013
$2.8M
Optimization of HPMPA and CDV Analogs for Treatment of SmallpoxR01AI074057 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI HOSTETLER, KARL Y · 2008 to 2011
$2.2M
ANALOGS OF HPMPA FOR TREATMENT OF SMALLPOXR01AI066499 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI HOSTETLER, KARL Y · 2005 to 2005
$1.4M
POTENT NEW NUCLEOSIDE ANALOGS FOR DRUG RESISTANT HIVR01AI071803 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI HOSTETLER, KARL Y · 2007 to 2010
$1.3M
CIHRNIAID NIH HHS AI-066499NIAID NIH HHS AI-071803NIAID NIH HHS AI-074057NIAID NIH HHS AI-076558NIAID NIH HHS R01 AI066499NIAID NIH HHS R01 AI071803NIAID NIH HHS R01 AI074057NIAID NIH HHS R01 AI076558
6 · The paper itself

Abstract

Cidofovir (1(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine, CDV) is a potent inhibitor of orthopoxvirus DNA replication. Prior studies have shown that, when CDV is incorporated into a growing primer strand, it can inhibit both the 3'-to-5' exonuclease and the 5'-to-3' chain extension activities of vaccinia virus DNA polymerase. This drug can also be incorporated into DNA, creating a significant impediment to trans-lesion DNA synthesis in a manner resembling DNA damage. CDV and deoxycytidine share a common nucleobase, but CDV lacks the deoxyribose sugar. The acyclic phosphonate bears a hydroxyl moiety that is equivalent to the 3'-hydroxyl of dCMP and permits CDV incorporation into duplex DNA. To study the structural consequences of inserting CDV into DNA, we have used (1)H NMR to solve the solution structures of a dodecamer DNA duplex containing a CDV molecule at position 7 and of a control DNA duplex. The overall structures of both DNA duplexes were found to be very similar. We observed a decrease of intensity (>50%) for the imino protons neighboring the CDV (G6, T8) and the cognate base G18 and a large chemical shift change for G18. This indicates higher proton exchange rates for this region, which were confirmed using NMR-monitored melting experiments. DNA duplex melting experiments monitored by circular dichroism revealed a lower T(m) for the CDV DNA duplex (46 °C) compared to the control (58 °C) in 0.2 M salt. Our results suggest that the CDV drug is well accommodated and stable within the dodecamer DNA duplex, but the stability of the complex is less than that of the control, suggesting increased dynamics around the CDV.

Indexed as

PoxviridaeAntiviral AgentsBase SequenceCidofovirCytosineDNADNA ReplicationMagnetic Resonance SpectroscopyMolecular Sequence DataMolecular StructureOrganophosphonatesSolutionsAntiviral AgentsCidofovirCytosineDNAOrganophosphonatesSolutions

Identifiers

PMID21280608
PMCPMC3051402
OpenAlexW2167017024

What OpenQuestion holds

Textmetadata
LicenceTDM
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.