Evidence map›Paper›PMID 37276386›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Real-time label-free detection of dynamic aptamer-small molecule interactions using a nanopore nucleic acid conformational sensor.

Rugare G Chingarande, Kai Tian, Yu Kuang, Aby Sarangee, Chengrui Hou, Emily Ma, Jarett Ren, Sam Hawkins, Joshua Kim, Ray Adelstein and 3 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

19 citing papers in PubMed, 38 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

13 authors at 1 institution in 1 country.

Rugare G ChingarandeDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.
Kai TianDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.ORCID 0000-0002-5543-571X
Yu KuangDalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211.
Aby SarangeeDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.
Chengrui HouDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.
Emily MaDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.
Jarett RenDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.
Sam HawkinsDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.ORCID 0000-0003-2595-2051
Joshua KimDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.
Ray AdelsteinDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.
Sally ChenDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.ORCID 0009-0006-7375-9183
Kevin D GillisDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.ORCID 0000-0003-0274-2270
Li-Qun GuDepartment of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211.ORCID 0000-0002-8710-6160
University of Missouri · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nucleic acids can undergo conformational changes upon binding small molecules. These conformational changes can be exploited to develop new therapeutic strategies through control of gene expression or triggering of cellular responses and can also be used to develop sensors for small molecules such as neurotransmitters. Many analytical approaches can detect dynamic conformational change of nucleic acids, but they need labeling, are expensive, and have limited time resolution. The nanopore approach can provide a conformational snapshot for each nucleic acid molecule detected, but has not been reported to detect dynamic nucleic acid conformational change in response to small -molecule binding. Here we demonstrate a modular, label-free, nucleic acid-docked nanopore capable of revealing time-resolved, small molecule-induced, single nucleic acid molecule conformational transitions with millisecond resolution. By using the dopamine-, serotonin-, and theophylline-binding aptamers as testbeds, we found that these nucleic acids scaffolds can be noncovalently docked inside the MspA protein pore by a cluster of site-specific charged residues. This docking mechanism enables the ion current through the pore to characteristically vary as the aptamer undergoes conformational changes, resulting in a sequence of current fluctuations that report binding and release of single ligand molecules from the aptamer. This nanopore tool can quantify specific ligands such as neurotransmitters, elucidate nucleic acid-ligand interactions, and pinpoint the nucleic acid motifs for ligand binding, showing the potential for small molecule biosensing, drug discovery assayed via RNA and DNA conformational changes, and the design of artificial riboswitch effectors in synthetic biology.

Indexed as

Aptamers, NucleotideNanoporesRiboswitchLigandsNucleic Acid ConformationRNAAptamers, NucleotideLigandsRiboswitchRNAaptamernanoporeneurotransmitter sensorRNA conformation dynamicssingle-molecule detection

Identifiers

PMID37276386
PMCPMC10268594
OpenAlexW4379468539

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.