ID | 113787 |
Title Alternative | pH-resistant Inhibitor of Mitochondrial ADP/ATP Carrier
|
Author |
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
Ohkura, Kazuto
Suzuka University of Medical Science
Shindo, Mitsuru
Kyushu University
|
Keywords | ADP/ATP carrier
bongkrekic acid(BKA)
mitochondria
mitochondrial solute carrier (SLC25a)
|
Content Type |
Journal Article
|
Description | 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.
|
Journal Title |
Chemical Biology & Drug Design
|
ISSN | 17470277
17470285
|
NCID | AA12108214
AA12571955
|
Publisher | John Wiley & Sons
|
Volume | 86
|
Issue | 5
|
Start Page | 1304
|
End Page | 1322
|
Published Date | 2015-05-29
|
Rights | 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.
|
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
|
TextVersion |
Author
|
departments |
Institute of Advanced Medical Sciences
|