Evidence map›Paper›PMID 29048375›Full record

ArticleMolecules (Basel, Switzerland)2017

Construction of a Bivalent Thrombin Binding Aptamer and Its Antidote with Improved Properties.

Quintin W Hughes, Bao T Le, Grace Gilmore, Ross I Baker, Rakesh N Veedu

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

14 citing papers in PubMed, 30 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

5 authors at 2 institutions in 1 country.

Quintin W HughesWestern Australian Centre for Thrombosis and Haemostasis, Discovery Way, Murdoch University, Perth, WA 6150, Australia. q.hughes@wacth.org.
Bao T LeCentre for Comparative Genomics, Discovery Way, Murdoch University, Perth, WA 6150, Australia. T.Le2@murdoch.edu.au.
Grace GilmoreWestern Australian Centre for Thrombosis and Haemostasis, Discovery Way, Murdoch University, Perth, WA 6150, Australia. g.gilmore@wacth.org.
Ross I BakerWestern Australian Centre for Thrombosis and Haemostasis, Discovery Way, Murdoch University, Perth, WA 6150, Australia. ross@haemwest.com.au.
Rakesh N VeeduCentre for Comparative Genomics, Discovery Way, Murdoch University, Perth, WA 6150, Australia. rveedu@ccg.murdoch.edu.au.
Murdoch University · AUHollywood Private Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson-Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of the human thrombin molecule, respectively, have been extensively studied due to their anticoagulant potentials. However, a fundamental issue preventing the clinical translation of many aptamers is degradation by nucleases and reduced pharmacokinetic properties requiring higher dosing regimens more often. In this study, we have chemically modified the design of previously described thrombin binding aptamers targeting exosites I, HD1, and exosite II, HD22. The individual aptamers were first modified with an inverted deoxythymidine nucleotide, and then constructed bivalent aptamers by connecting the HD1 and HD22 aptamers either through a triethylene glycol (TEG) linkage or four consecutive deoxythymidines together with an inverted deoxythymidine nucleotide at the 3'-end. The anticoagulation potential, the reversal of coagulation with different antidote sequences, and the nuclease stability of the aptamers were then investigated. The results showed that a bivalent aptamer RNV220 containing an inverted deoxythymidine and a TEG linkage chemistry significantly enhanced the anticoagulation properties in blood plasma and nuclease stability compared to the existing aptamer designs. Furthermore, a bivalent antidote sequence RNV220AD efficiently reversed the anticoagulation effect of RNV220 in blood plasma. Based on our results, we believe that RNV220 could be developed as a potential anticoagulant therapeutic molecule.

Indexed as

AntidotesAptamers, NucleotideBinding SitesBlood CoagulationDeoxyribonucleasesHumansMolecular StructureThrombinAntidotesAptamers, NucleotideDeoxyribonucleasesThrombinaptamermodified nucleotidethrombin binding aptamertriethylene glycol linkage

Identifiers

PMID29048375
PMCPMC6151750
OpenAlexW2766983864

What OpenQuestion holds

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LicenceCC BY
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.