Ion channel complex of antibiotics as viewed by NMR

Michio Murata, Yusuke Kasai, Yuichi Umegawa, Naohiro Matsushita, Hiroshi Tsuchikawa, Nobuaki Matsumori, Tohru Oishi

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13 Citations (Scopus)

Abstract

Amphotericin B (AmB) exerts its pharmacological effects by forming a barrel-stave assembly in fungal membranes. To examine the interaction between AmB and ergosterol or cholesterol, 13C- and 19F-labeled covalent conjugates were prepared and subjected to solidstate NMR measurements. Using rotor-synchronous double-resonance experiments such as rotational echo double resonance (REDOR) and RDX, we estimated the distance between the fluorine atom and its nearest carbon in the heptaene moiety to be less than 8.6 A ̊, indicating that the B ring of ergosterol comes close to the AmB polyene moiety. Conformational search of the AmB-ergosterol conjugate using the NMR-derived constraints suggested that ergosterol molecules surround the AmB assembly in contrast to the conventional image where ergosterol is inserted into AmB molecules. AmB-AmB bimolecular interaction was examined by using 13C- and 19F-labeled AmBs in dimyritoylphosphatidylcholine (DMPC) membrane without sterols. 13C- and 19F dipolar interactions deriving from both head-to-head and head-to-tail orientations were observed in the REDOR experiments. The interactions between AmB and acyl chains of the phospholipid were also detected.

Original languageEnglish
Pages (from-to)1123-1129
Number of pages7
JournalPure and Applied Chemistry
Volume81
Issue number6
DOIs
Publication statusPublished - Jul 24 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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    Murata, M., Kasai, Y., Umegawa, Y., Matsushita, N., Tsuchikawa, H., Matsumori, N., & Oishi, T. (2009). Ion channel complex of antibiotics as viewed by NMR. Pure and Applied Chemistry, 81(6), 1123-1129. https://doi.org/10.1351/PAC-CON-08-08-37