Agonist/Antagonist Activity of Oxytocin Variants Obtained from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
23 Nov 2021
23 Nov 2021
Historique:
received:
09
09
2021
accepted:
21
10
2021
entrez:
29
11
2021
pubmed:
30
11
2021
medline:
30
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34841168
doi: 10.1021/acsomega.1c04982
pmc: PMC8613857
doi:
Types de publication
Journal Article
Langues
eng
Pagination
31244-31252Informations de copyright
© 2021 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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