Development of a selective agonist for relaxin family peptide receptor 3

Abstract Relaxin family peptides perform a variety of biological functions by activating four G protein-coupled receptors, namely RXFP1–4. Among these receptors, RXFP3 lacks a specific natural or synthetic agonist at present. A previously designed chimeric R3/I5 peptide, consisting of the B-chain of...

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Autores principales:	Dian Wei, Meng-Jun Hu, Xiao-Xia Shao, Jia-Hui Wang, Wei-Han Nie, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd1d78fe5c3a428ab981eb57cc8c7a40
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spelling	oai:doaj.org-article:cd1d78fe5c3a428ab981eb57cc8c7a402021-12-02T11:53:14ZDevelopment of a selective agonist for relaxin family peptide receptor 310.1038/s41598-017-03465-72045-2322https://doaj.org/article/cd1d78fe5c3a428ab981eb57cc8c7a402017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03465-7https://doaj.org/toc/2045-2322Abstract Relaxin family peptides perform a variety of biological functions by activating four G protein-coupled receptors, namely RXFP1–4. Among these receptors, RXFP3 lacks a specific natural or synthetic agonist at present. A previously designed chimeric R3/I5 peptide, consisting of the B-chain of relaxin-3 and the A-chain of INSL5, displays equal activity towards the homologous RXFP3 and RXFP4. To increase its selectivity towards RXFP3, in the present study we conducted extensive mutagenesis around the B-chain C-terminal region of R3/I5. Decreasing or increasing the peptide length around the B23–B25 position dramatically lowered the activation potency of R3/I5 towards both RXFP3 and RXFP4. Substitution of B23Gly with Ala or Ser converted R3/I5 from an efficient agonist to a strong antagonist for RXFP3, but the mutants retained considerable activation potency towards RXFP4. Substitution of B24Gly increased the selectivity of R3/I5 towards RXFP3 over the homologous RXFP4. The best mutant, [G(B24)S]R3/I5, displayed 20-fold higher activation potency towards RXFP3 than towards RXFP4, meanwhile retained full activation potency at RXFP3. Thus, [G(B24)S]R3/I5 is the best RXFP3-selective agonist known to date. It is a valuable tool for investigating the physiological functions of RXFP3, and also a suitable template for developing RXFP3-specific agonists in future.Dian WeiMeng-Jun HuXiao-Xia ShaoJia-Hui WangWei-Han NieYa-Li LiuZeng-Guang XuZhan-Yun GuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dian Wei Meng-Jun Hu Xiao-Xia Shao Jia-Hui Wang Wei-Han Nie Ya-Li Liu Zeng-Guang Xu Zhan-Yun Guo Development of a selective agonist for relaxin family peptide receptor 3
description	Abstract Relaxin family peptides perform a variety of biological functions by activating four G protein-coupled receptors, namely RXFP1–4. Among these receptors, RXFP3 lacks a specific natural or synthetic agonist at present. A previously designed chimeric R3/I5 peptide, consisting of the B-chain of relaxin-3 and the A-chain of INSL5, displays equal activity towards the homologous RXFP3 and RXFP4. To increase its selectivity towards RXFP3, in the present study we conducted extensive mutagenesis around the B-chain C-terminal region of R3/I5. Decreasing or increasing the peptide length around the B23–B25 position dramatically lowered the activation potency of R3/I5 towards both RXFP3 and RXFP4. Substitution of B23Gly with Ala or Ser converted R3/I5 from an efficient agonist to a strong antagonist for RXFP3, but the mutants retained considerable activation potency towards RXFP4. Substitution of B24Gly increased the selectivity of R3/I5 towards RXFP3 over the homologous RXFP4. The best mutant, [G(B24)S]R3/I5, displayed 20-fold higher activation potency towards RXFP3 than towards RXFP4, meanwhile retained full activation potency at RXFP3. Thus, [G(B24)S]R3/I5 is the best RXFP3-selective agonist known to date. It is a valuable tool for investigating the physiological functions of RXFP3, and also a suitable template for developing RXFP3-specific agonists in future.
format	article
author	Dian Wei Meng-Jun Hu Xiao-Xia Shao Jia-Hui Wang Wei-Han Nie Ya-Li Liu Zeng-Guang Xu Zhan-Yun Guo
author_facet	Dian Wei Meng-Jun Hu Xiao-Xia Shao Jia-Hui Wang Wei-Han Nie Ya-Li Liu Zeng-Guang Xu Zhan-Yun Guo
author_sort	Dian Wei
title	Development of a selective agonist for relaxin family peptide receptor 3
title_short	Development of a selective agonist for relaxin family peptide receptor 3
title_full	Development of a selective agonist for relaxin family peptide receptor 3
title_fullStr	Development of a selective agonist for relaxin family peptide receptor 3
title_full_unstemmed	Development of a selective agonist for relaxin family peptide receptor 3
title_sort	development of a selective agonist for relaxin family peptide receptor 3
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cd1d78fe5c3a428ab981eb57cc8c7a40
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Development of a selective agonist for relaxin family peptide receptor 3

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