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Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3.

ABSTRACT: T1R2/T1R3 belongs to G protein coupled receptors, which recognizes diverse natural and synthetic sweeteners. A novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 was identified through high-throughput screening campaign. Comparing the structure of the potent compound with previously known PAM, we classified the structure of known PAM into three parts, defined as "head", "linker", and "tail". We then investigated the linker-tail structure. It was suggested by molecular docking models of T1R2/T1R3 that an amine that we introduced in the tail was the key for interaction with the receptor binding pocket. We thus synthesized various molecules and found unnatural tripeptide-PAMs, which potently enhance the sweetness of sucrose in sensory evaluation tests.

SUBMITTER: Yamada K

PROVIDER: S-EPMC6511967 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3.

Yamada Kei K Nakazawa Masakazu M Matsumoto Kayo K Tagami Uno U Hirokawa Takatsugu T Homma Keisuke K Mori Suguru S Matsumoto Ryo R Saikawa Wakana W Kitajima Seiji S

ACS medicinal chemistry letters 20190325 5

T1R2/T1R3 belongs to G protein coupled receptors, which recognizes diverse natural and synthetic sweeteners. A novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 was identified through high-throughput screening campaign. Comparing the structure of the potent compound with previously known PAM, we classified the structure of known PAM into three parts, defined as "head", "linker", and "tail". We then investigated the linker-tail structure. It was suggested by molecular docking mode ...[more]

PMID: 31098002

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