Design, synthesis and evaluation of unnatural peptides as T1R2/T1R3 PAMs.


Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 04 2020
Historique:
received: 21 11 2019
revised: 21 01 2020
accepted: 24 01 2020
pubmed: 18 2 2020
medline: 1 5 2021
entrez: 18 2 2020
Statut: ppublish

Résumé

The sweet receptor T1R2/T1R3 is a member of G protein-coupled receptor family and recognizes diverse natural and synthetic sweeteners. Previously, we reported a novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 comprising an unnatural tripeptide structure. We classified the structure of these PAMs into three parts: "head", "linker" and "tail". Here, we report the design, synthesis and evaluation of various tail structures to obtain highly active unnatural peptide structure of PAM. In conclusion, we discovered the novel unnatural tetrapeptide with highly potent PAM activity on T1R2/T1R3 in a cell-based assay system.

Identifiants

pubmed: 32063432
pii: S0960-894X(20)30063-9
doi: 10.1016/j.bmcl.2020.127000
pii:
doi:

Substances chimiques

Peptides 0
Receptors, G-Protein-Coupled 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

127000

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Kei Yamada (K)

Ajinomoto Co., Inc., 1-1, Suzuki-Cho, Kawasaki-Ku, Kawasaki-Shi 210-8681, Japan. Electronic address: kei_yamada@ajinomoto.com.

Ryo Matsumoto (R)

Ajinomoto Co., Inc., 1-1, Suzuki-Cho, Kawasaki-Ku, Kawasaki-Shi 210-8681, Japan.

Yumiko Suzuki (Y)

Ajinomoto Co., Inc., 1-1, Suzuki-Cho, Kawasaki-Ku, Kawasaki-Shi 210-8681, Japan.

Suguru Mori (S)

Ajinomoto Co., Inc., 1-1, Suzuki-Cho, Kawasaki-Ku, Kawasaki-Shi 210-8681, Japan.

Seiji Kitajima (S)

Ajinomoto Co., Inc., 1-1, Suzuki-Cho, Kawasaki-Ku, Kawasaki-Shi 210-8681, Japan.

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Classifications MeSH