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Agonist/Antagonist Activity of Oxytocin Variants Obtained from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution
[Image: see text] We established a method for synthesizing a free cyclic peptide library via peptide array synthesis to demonstrate the sequence activity of cyclic peptides. Variants of the cyclic nonapeptide oxytocin (OXT) were synthesized via residue substitution. Natural amino acids (AAs) were cl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613857/ https://www.ncbi.nlm.nih.gov/pubmed/34841168 http://dx.doi.org/10.1021/acsomega.1c04982 |
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author | Kinoshita, Remi Kozaki, Ikko Shimizu, Kazunori Shibata, Takahiro Ochiai, Akihito Honda, Hiroyuki |
author_facet | Kinoshita, Remi Kozaki, Ikko Shimizu, Kazunori Shibata, Takahiro Ochiai, Akihito Honda, Hiroyuki |
author_sort | Kinoshita, Remi |
collection | PubMed |
description | [Image: see text] We established a method for synthesizing a free cyclic peptide library via peptide array synthesis to demonstrate the sequence activity of cyclic peptides. Variants of the cyclic nonapeptide oxytocin (OXT) were synthesized via residue substitution. Natural amino acids (AAs) were classified into eight groups based on their physical properties and the size of their side chains, and a representative AA from each group was selected for residue substitution. All OXT variants were systematically evaluated for agonist/antagonist activity. Consequently, no improvement in agonist activity was observed, although substitution of the P4 and P8 residues resulted in decreased activity due to AA substitution. A few OXT variants exhibited antagonistic activity. In particular, the variants with P2 Leu residue substitution (Y2L) and Phe substitutions at residues 4 (Q4F), 5 (N5F), and 7 (P7F) showed high antagonistic activity. Variant Y2W was found to have the highest inhibitory effect, with a dissociation constant of 44 nM, which was comparable to that of the commercial antagonist atosiban (21 nM). Therefore, a free cyclic peptide library constructed via substitution with a natural AA residue was confirmed to be a powerful tool for bioactive peptide screening. |
format | Online Article Text |
id | pubmed-8613857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-86138572021-11-26 Agonist/Antagonist Activity of Oxytocin Variants Obtained from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution Kinoshita, Remi Kozaki, Ikko Shimizu, Kazunori Shibata, Takahiro Ochiai, Akihito Honda, Hiroyuki ACS Omega [Image: see text] We established a method for synthesizing a free cyclic peptide library via peptide array synthesis to demonstrate the sequence activity of cyclic peptides. Variants of the cyclic nonapeptide oxytocin (OXT) were synthesized via residue substitution. Natural amino acids (AAs) were classified into eight groups based on their physical properties and the size of their side chains, and a representative AA from each group was selected for residue substitution. All OXT variants were systematically evaluated for agonist/antagonist activity. Consequently, no improvement in agonist activity was observed, although substitution of the P4 and P8 residues resulted in decreased activity due to AA substitution. A few OXT variants exhibited antagonistic activity. In particular, the variants with P2 Leu residue substitution (Y2L) and Phe substitutions at residues 4 (Q4F), 5 (N5F), and 7 (P7F) showed high antagonistic activity. Variant Y2W was found to have the highest inhibitory effect, with a dissociation constant of 44 nM, which was comparable to that of the commercial antagonist atosiban (21 nM). Therefore, a free cyclic peptide library constructed via substitution with a natural AA residue was confirmed to be a powerful tool for bioactive peptide screening. American Chemical Society 2021-11-08 /pmc/articles/PMC8613857/ /pubmed/34841168 http://dx.doi.org/10.1021/acsomega.1c04982 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Kinoshita, Remi Kozaki, Ikko Shimizu, Kazunori Shibata, Takahiro Ochiai, Akihito Honda, Hiroyuki Agonist/Antagonist Activity of Oxytocin Variants Obtained from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution |
title | Agonist/Antagonist Activity of Oxytocin Variants Obtained
from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution |
title_full | Agonist/Antagonist Activity of Oxytocin Variants Obtained
from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution |
title_fullStr | Agonist/Antagonist Activity of Oxytocin Variants Obtained
from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution |
title_full_unstemmed | Agonist/Antagonist Activity of Oxytocin Variants Obtained
from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution |
title_short | Agonist/Antagonist Activity of Oxytocin Variants Obtained
from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution |
title_sort | agonist/antagonist activity of oxytocin variants obtained
from free cyclic peptide libraries generated via amino acid substitution |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613857/ https://www.ncbi.nlm.nih.gov/pubmed/34841168 http://dx.doi.org/10.1021/acsomega.1c04982 |
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