Evidence map›Paper›PMID 34880210›Full record

ArticleNature communications2021

Design of a methotrexate-controlled chemical dimerization system and its use in bio-electronic devices.

Zhong Guo, Oleh Smutok, Wayne A Johnston, Patricia Walden, Jacobus P J Ungerer, Thomas S Peat, Janet Newman, Jake Parker, Tom Nebl, Caryn Hepburn and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  6. Assessing structural prediction accuracy for nanobody-small molecule complexes.Protein engineering, design & selection : PEDS · 2026
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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

14 authors at 4 institutions in 2 countries.

Zhong GuoARC Centre of Excellence in Synthetic Biology, Sydney, NSW, Australia.
Oleh SmutokDepartment of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Ave., Potsdam, NY, 13699, USA.
Wayne A JohnstonCentre for Agriculture and the Bioeconomy, Queensland University of Technology, Brisbane, QLD, 4001, Australia.
Patricia WaldenCentre for Agriculture and the Bioeconomy, Queensland University of Technology, Brisbane, QLD, 4001, Australia.
Jacobus P J UngererDepartment of Chemical Pathology, Pathology Queensland, Brisbane, QLD, 4001, Australia.
Thomas S PeatBiology Group, Biomedical Manufacturing Program, CSIRO, 343 Royal Parade, Parkville, VIC, 3052, Australia.
Janet NewmanBiology Group, Biomedical Manufacturing Program, CSIRO, 343 Royal Parade, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0003-2666-3219
Jake ParkerCentre for Agriculture and the Bioeconomy, Queensland University of Technology, Brisbane, QLD, 4001, Australia.
Tom NeblBiology Group, Biomedical Manufacturing Program, CSIRO, 343 Royal Parade, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0003-4003-9340
Caryn HepburnWaters Australia Pty Ltd, 38-46 South Str, Rydalmere, NSW, 2116, Australia.
Artem MelmanDepartment of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Ave., Potsdam, NY, 13699, USA.
Richard J SudermanNectagen, Inc., 2002 W 39th Ave, Kansas City, KS, 66103, USA.
Evgeny KatzDepartment of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Ave., Potsdam, NY, 13699, USA.
Kirill AlexandrovARC Centre of Excellence in Synthetic Biology, Sydney, NSW, Australia. kirill.alexandrov@qut.edu.au.ORCID http://orcid.org/0000-0002-0957-6511
Queensland University of Technology · AUClarkson University · USCommonwealth Scientific and Industrial Research Organisation · AUQueensland Health · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Natural evolution produced polypeptides that selectively recognize chemical entities and their polymers, ranging from ions to proteins and nucleic acids. Such selective interactions serve as entry points to biological signaling and metabolic pathways. The ability to engineer artificial versions of such entry points is a key goal of synthetic biology, bioengineering and bioelectronics. We set out to map the optimal strategy for developing artificial small molecule:protein complexes that function as chemically induced dimerization (CID) systems. Using several starting points, we evolved CID systems controlled by a therapeutic drug methotrexate. Biophysical and structural analysis of methotrexate-controlled CID system reveals the critical role played by drug-induced conformational change in ligand-controlled protein complex assembly. We demonstrate utility of the developed CID by constructing electrochemical biosensors of methotrexate that enable quantification of methotrexate in human serum. Furthermore, using the methotrexate and functionally related biosensor of rapamycin we developed a multiplexed bioelectronic system that can perform repeated measurements of multiple analytes. The presented results open the door for construction of genetically encoded signaling systems for use in bioelectronics and diagnostics, as well as metabolic and signaling network engineering.

Indexed as

DimerizationElectronicsBiosensing TechniquesElectrochemistryHumansLigandsMethotrexatePeptidesPolymersProteinsLigandsMethotrexatePeptidesPolymersProteins

Identifiers

PMID34880210
PMCPMC8654847
OpenAlexW4200213192

What OpenQuestion holds

Textmetadata
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.