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Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders

BACKGROUND: Endothelin (ET)-traps are Fc-fusion proteins with a design based on the physiological receptors of ET-1. Previous work has shown that use of the selected ET-traps potently and significantly reduces different markers of diabetes pathology back to normal, non-disease levels. AIM: To demons...

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Autores principales: Jain, Arjun, Bozovicar, Kristof, Mehrotra, Vidhi, Bratkovic, Tomaz, Johnson, Martin H, Jha, Ira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210543/
https://www.ncbi.nlm.nih.gov/pubmed/35800412
http://dx.doi.org/10.4239/wjd.v13.i6.434
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author Jain, Arjun
Bozovicar, Kristof
Mehrotra, Vidhi
Bratkovic, Tomaz
Johnson, Martin H
Jha, Ira
author_facet Jain, Arjun
Bozovicar, Kristof
Mehrotra, Vidhi
Bratkovic, Tomaz
Johnson, Martin H
Jha, Ira
author_sort Jain, Arjun
collection PubMed
description BACKGROUND: Endothelin (ET)-traps are Fc-fusion proteins with a design based on the physiological receptors of ET-1. Previous work has shown that use of the selected ET-traps potently and significantly reduces different markers of diabetes pathology back to normal, non-disease levels. AIM: To demonstrate the selected ET-traps potently and significantly bind to ET-1. METHODS: We performed phage display experiments to test different constructs of ET-traps, and conducted bio-layer interferometry binding assays to verify that the selected ET-traps bind specifically to ET-1 and display binding affinity in the double-digit picomolar range (an average of 73.8 rM, n = 6). RESULTS: These experiments have confirmed our choice of the final ET-traps and provided proof-of-concept for the potential use of constructs as effective biologics for diseases associated with pathologically elevated ET-1. CONCLUSION: There is increased need for such therapeutics as they could help save millions of lives around the world.
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spelling pubmed-92105432022-07-06 Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders Jain, Arjun Bozovicar, Kristof Mehrotra, Vidhi Bratkovic, Tomaz Johnson, Martin H Jha, Ira World J Diabetes Basic Study BACKGROUND: Endothelin (ET)-traps are Fc-fusion proteins with a design based on the physiological receptors of ET-1. Previous work has shown that use of the selected ET-traps potently and significantly reduces different markers of diabetes pathology back to normal, non-disease levels. AIM: To demonstrate the selected ET-traps potently and significantly bind to ET-1. METHODS: We performed phage display experiments to test different constructs of ET-traps, and conducted bio-layer interferometry binding assays to verify that the selected ET-traps bind specifically to ET-1 and display binding affinity in the double-digit picomolar range (an average of 73.8 rM, n = 6). RESULTS: These experiments have confirmed our choice of the final ET-traps and provided proof-of-concept for the potential use of constructs as effective biologics for diseases associated with pathologically elevated ET-1. CONCLUSION: There is increased need for such therapeutics as they could help save millions of lives around the world. Baishideng Publishing Group Inc 2022-06-15 2022-06-15 /pmc/articles/PMC9210543/ /pubmed/35800412 http://dx.doi.org/10.4239/wjd.v13.i6.434 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Jain, Arjun
Bozovicar, Kristof
Mehrotra, Vidhi
Bratkovic, Tomaz
Johnson, Martin H
Jha, Ira
Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
title Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
title_full Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
title_fullStr Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
title_full_unstemmed Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
title_short Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
title_sort investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210543/
https://www.ncbi.nlm.nih.gov/pubmed/35800412
http://dx.doi.org/10.4239/wjd.v13.i6.434
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