Evidence map›Paper›PMID 35213635›Full record

ArticlePloS one2022

Human IL-2Rɑ subunit binding modulation of IL-2 through a decline in electrostatic interactions: A computational and experimental approach.

Arezoo Beig Parikhani, Kowsar Bagherzadeh, Rada Dehghan, Alireza Biglari, Mohammad Ali Shokrgozar, Farhad Riazi Rad, Sirous Zeinali, Yeganeh Talebkhan, Soheila Ajdary, Reza Ahangari Cohan and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.0field-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

7 citing papers in PubMed, 14 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

11 authors at 3 institutions in 1 country.

Arezoo Beig ParikhaniVenom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Kowsar BagherzadehStem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran.
Rada DehghanVenom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Alireza BiglariSchool of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Ali ShokrgozarNational Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.ORCID 0000-0002-9198-4070
Farhad Riazi RadDepartment of Immunology, Pasteur Institute of Iran, Tehran, Iran.
Sirous ZeinaliMolecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Yeganeh TalebkhanDepartment of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Soheila AjdaryDepartment of Immunology, Pasteur Institute of Iran, Tehran, Iran.ORCID 0000-0002-5052-2523
Reza Ahangari CohanDepartment of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran.ORCID 0000-0002-0490-4184
Mahdi BehdaniVenom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.ORCID 0000-0002-4839-5123
Pasteur Institute of Iran · IRIran University of Medical Sciences · IRTehran University of Medical Sciences · IR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although high-dose IL-2 has clear antitumor effects, severe side effects like severe toxicity and activation of Tregs by binding of IL-2 to high-affinity IL-2R, hypotension, and vascular leak syndrome limit its applications as a therapeutic antitumor agent. Here in this study, a rational computational approach was employed to develop and design novel triple-mutant IL-2 variants with the aim of improving IL-2-based immunotherapy. The affinity of the mutants towards IL-2Rα was further computed with the aid of molecular dynamic simulations and umbrella sampling techniques and the obtained results were compared to those of wild-type IL-2. In vitro experiments by flow cytometry showed that the anti-CD25 mAb was able to bind to PBMC cells even after mutant 2 preincubation, however, the binding strength of the mutant to α-subunit was less than of wtIL-2. Additionally, reduction of IL-2Rα subunit affinity did not significantly disturb IL-2/IL2Rβγc subunits interactions.

Indexed as

Interleukin-2 Receptor alpha SubunitMolecular Docking SimulationMolecular Dynamics SimulationStatic ElectricityHumansInterleukin-2Leukocytes, MononuclearProtein BindingIL2 protein, humanIL2RA protein, humanInterleukin-2Interleukin-2 Receptor alpha Subunit

Identifiers

PMID35213635
PMCPMC8880607
OpenAlexW4214503602

What OpenQuestion holds

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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.