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2019 Fiscal Year Final Research Report

Development of artificial antibody of anti-bitter taste receptor using random amino acid sequence library

Research Project

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Project/Area Number 16K08426
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionMukogawa Women's University

Principal Investigator

Uchida Takahiro  武庫川女子大学, 薬学部, 教授 (70203536)

Co-Investigator(Kenkyū-buntansha) 吉田 都  武庫川女子大学, 薬学部, 准教授 (20369028)
伊東 祐二  鹿児島大学, 理工学域理学系, 教授 (60223195)
Project Period (FY) 2016-04-01 – 2020-03-31
Keywords味覚センサ / Asp-Asp / Glu-Glu / アスパラギン酸 / グルタミン酸 / hTAS2R14 / 表面プラズモン共鳴 / 分子モデリング
Outline of Final Research Achievements

We firstly found the correlation between taste sensor output of commercial medicines and their response in various type of human receptors. Secondly, the inhibition of Asp-Asp and Glu-Glu as umami-peptides and their constituent Asp and Glu as amino acid toward 0.5 mM diphenhydramine hydrochloride (DPH) solution were examined. The Asp-Asp and Glu-Glu dramatically reduced bitterness sensor output of DPH in their concentration dependent manner. In the SPR experiment, the spectrum change was ranked as follows: Asp-Asp>Glu-Glu>Asp>Glu. This information and docking simulation study suggested that competitive inhibition of umami-peptide via binding to binding site of hTAS2R14

Free Research Field

医療系薬学

Academic Significance and Societal Importance of the Research Achievements

苦味を呈する医薬品は苦味受容体タンパク(hTAS2R10、hTAS2R14他)の基質であることが確認されているが特異的な苦味抑制剤は開発されていない。研究代表者は多くのペプチド、アミノ酸類の中から旨味ペプチドに着目し、塩基性薬物への有意な苦味抑制効果を味覚センサで検証し、その機序について表面プラズモン共鳴 (SPR)と分子モデリングにより予測した。検討により多くの塩基性薬物について比較的低分子のAsp-Asp、Glu-GluならびにAsp、Gluが一定の苦味抑制効果を示すことを見出した点に本研究の意義がある。今後分子モデリングの活用により苦味受容体のインバースアゴニストの分子設計に応用できる。

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Published: 2021-02-19  

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