Evidence map›Paper›PMID 27566147›Full record

ArticleNucleic acids research2016

Evoking picomolar binding in RNA by a single phosphorodithioate linkage.

N Dinuka Abeydeera, Martin Egli, Nehemiah Cox, Karen Mercier, Jonas Nascimento Conde, Pradeep S Pallan, Daniella M Mizurini, Malgorzata Sierant, Fatima-Ezzahra Hibti, Tom Hassell and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 119 citations in OpenAlex.

  1. Review
  2. Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  3. Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025
    Review
  4. Enhanced Control of Liposomal Drug Release by Drug-Aptamer Complexes.Advanced materials (Deerfield Beach, Fla.) · 2025
    Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  14. Review
  15. Review
  16. Article
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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

21 authors at 11 institutions in 5 countries.

N Dinuka AbeydeeraAM Biotechnologies, LLC, 12521 Gulf Freeway, Houston, TX 77034, USA.
Martin EgliDepartment of Biochemistry, Vanderbilt University, School of Medicine, Nashville, TN 37232, USA martin.egli@vanderbilt.edu.
Nehemiah CoxDepartment of Biology, Texas A&M University, College Station, TX 77843, USA.
Karen MercierBiointeractions Division, Horiba Scientific, Avenue de la Vauve - Passage JobinYvon CS 45002 Palaiseau, France.
Jonas Nascimento CondeInstituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941, Brazil.
Pradeep S PallanDepartment of Biochemistry, Vanderbilt University, School of Medicine, Nashville, TN 37232, USA.
Daniella M MizuriniInstituto de Bioquimica Médica Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941, Brazil.
Malgorzata SierantDepartment of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 90-363 Lodz, Sienkiewicza 112, Poland.
Fatima-Ezzahra HibtiBiointeractions Division, Horiba Scientific, Avenue de la Vauve - Passage JobinYvon CS 45002 Palaiseau, France.
Tom HassellMilliporeSigma, 9186 Six Pines, The Woodlands, TX 77380, USA.
Tianzhi WangThe Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Feng-Wu LiuSchool of Pharmaceutical Sciences, Zhengzhou University, Science Avenue 100, Zhengzhou 450001, Henan, China.
Hong-Min LiuSchool of Pharmaceutical Sciences, Zhengzhou University, Science Avenue 100, Zhengzhou 450001, Henan, China.
Carlos MartinezMilliporeSigma, 9186 Six Pines, The Woodlands, TX 77380, USA.
Anil K SoodDepartments of Gynecologic Oncology and Cancer Biology, and Center for RNAi and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Terry P LybrandDepartments of Chemistry and Pharmacology, and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.
Chiraz FrydmanBiointeractions Division, Horiba Scientific, Avenue de la Vauve - Passage JobinYvon CS 45002 Palaiseau, France.
Robson Q MonteiroInstituto de Bioquimica Médica Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941, Brazil.
Richard H GomerDepartment of Biology, Texas A&M University, College Station, TX 77843, USA.
Barbara NawrotDepartment of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 90-363 Lodz, Sienkiewicza 112, Poland.
Xianbin YangAM Biotechnologies, LLC, 12521 Gulf Freeway, Houston, TX 77034, USA Xianbin.yang@thioaptamer.com xianbin@hotmail.com.
Horiba (France) · FRUniversidade Federal do Rio de Janeiro · BRVanderbilt University · USRaptamer Discovery Group (United States) · USTexas A&M University · USTorrey Pines Institute For Molecular Studies · USZhengzhou University · CNCentrum Badań Molekularnych i Makromolekularnych Polskiej Akademii Nauk · PLPolish Academy of Sciences · PLThe University of Texas MD Anderson Cancer Center · USThe University of Texas Medical Branch at Galveston · US

Funding

New Reagents for the Synthesis of Phosphorodithioate-Modified 2'-O-Methyl RNAsR43GM086937 · NIGMS · AM BIOTECHNOLOGIES, LLC · PI DURLAND, ROSS HOWARD, YANG, XIANBIN · 2011 to 2011
$157k
NIGMS NIH HHS R43 GM086937
6 · The paper itself

Abstract

RNA aptamers are synthetic oligonucleotide-based affinity molecules that utilize unique three-dimensional structures for their affinity and specificity to a target such as a protein. They hold the promise of numerous advantages over biologically produced antibodies; however, the binding affinity and specificity of RNA aptamers are often insufficient for successful implementation in diagnostic assays or as therapeutic agents. Strong binding affinity is important to improve the downstream applications. We report here the use of the phosphorodithioate (PS2) substitution on a single nucleotide of RNA aptamers to dramatically improve target binding affinity by ∼1000-fold (from nanomolar to picomolar). An X-ray co-crystal structure of the α-thrombin:PS2-aptamer complex reveals a localized induced-fit rearrangement of the PS2-containing nucleotide which leads to enhanced target interaction. High-level quantum mechanical calculations for model systems that mimic the PS2 moiety and phenylalanine demonstrate that an edge-on interaction between sulfur and the aromatic ring is quite favorable, and also confirm that the sulfur analogs are much more polarizable than the corresponding phosphates. This favorable interaction involving the sulfur atom is likely even more significant in the full aptamer-protein complexes than in the model systems.

Indexed as

Aptamers, NucleotideCell LineHumansKineticsLimit of DetectionModels, MolecularNucleic Acid ConformationPhosphatesProtein BindingProteinsReference StandardsRNARNA StabilitySerumThermodynamicsVascular Endothelial Growth Factor AAptamers, NucleotidePhosphatesphosphorodithioic acidProteinsRNAVascular Endothelial Growth Factor A

Identifiers

PMID27566147
PMCPMC5041495
OpenAlexW2515015400

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.