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ID 113787
タイトル別表記
pH-resistant Inhibitor of Mitochondrial ADP/ATP Carrier
著者
Yamamoto, Atsushi Suzuka University of Medical Science
Hasui, Keisuke Kyushu University
Matsuo, Hiroshi Kyushu University
Okuda, Katsuhiro Kyushu University
Abe, Masato Kyushu University
Matsumoto, Kenji Kyushu University
Harada, Kazuki Tokushima University
Yoshimura, Yuya Tokushima University
大倉, 一人 Suzuka University of Medical Science
新藤, 充 Kyushu University
キーワード
ADP/ATP carrier
bongkrekic acid(BKA)
mitochondria
mitochondrial solute carrier (SLC25a)
資料タイプ
学術雑誌論文
抄録
Bongkrekic acid (BKA), isolated from Burkholderia cocovenenans, is known to specifically inhibit the mitochondrial ADP/ATP carrier. However, the manner of its interaction with the carrier remains elusive. In the present study, we tested the inhibitory effects of 17 bongkrekic acid analogues, derived from the intermediates obtained during its total synthesis, on the mitochondrial ATP/ATP carrier. Rough screening of these chemicals, done by measuring their inhibitory effects on the mitochondrial ATP synthesis, revealed that 4 of them, KH-1, 7, 16, and 17, had moderate inhibitory effects. Further characterization of the actions of these 4 analogues on mitochondrial function showed that KH-16 had moderate; KH-1 and KH-17, weak; and KH-7, negligible side effects of both permeabilization of the mitochondrial inner membrane and inhibition of the electron transport, indicating that only KH-7 had a specific inhibitory effect on the mitochondrial ADP/ATP carrier. Although the parental bongkrekic acid showed a strong pH dependency of its action, the inhibitory effect of KH-7 was almost insensitive to the pH of the reaction medium, indicating the importance of the 3 carboxyl groups of BKA for its pH- dependent action. A direct inhibitory effect of KH-7 on the mitochondrial ADP/ATP carrier was also clearly demonstrated.
掲載誌名
Chemical Biology & Drug Design
ISSN
17470277
17470285
cat書誌ID
AA12108214
AA12571955
出版者
John Wiley & Sons
86
5
開始ページ
1304
終了ページ
1322
発行日
2015-05-29
権利情報
This is the peer reviewed version of the following article: Yamamoto, A. , Hasui, K. , Matsuo, H. , Okuda, K. , Abe, M. , Matsumoto, K. , Harada, K. , Yoshimura, Y. , Yamamoto, T. , Ohkura, K. , Shindo, M. and Shinohara, Y. (2015), Bongkrekic Acid Analogue, Lacking One of the Carboxylic Groups of its Parent Compound, Shows Moderate but pH‐insensitive Inhibitory Effects on the Mitochondrial ADP/ATP Carrier. Chem Biol Drug Des, 86: 1304-1322, which has been published in final form at https://doi.org/10.1111/cbdd.12594. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
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フルテキストファイル
言語
eng
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著者版
部局
先端酵素学研究所