Possible conformation of amphotericin B dimer in membrane-bound assembly as deduced from solid-state NMR

Yuichi Umegawa; Takeshi Adachi; Nobuaki Matsumori; Michio Murata

doi:10.1016/j.bmc.2012.08.016

Possible conformation of amphotericin B dimer in membrane-bound assembly as deduced from solid-state NMR

Yuichi Umegawa
, Takeshi Adachi
, Nobuaki Matsumori
, Michio Murata

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Aiming for structural analysis of amphotericin B (AmB) ion-channel assemblies in membrane, a covalent dimer was synthesized between ¹³C-labled AmB methyl ester and ¹⁹F-labled AmB. The dimer showed slightly weaker but significant biological activities against fungi and red blood cells compared with those of monomeric AmB. Then the dimer was subjected to ¹³C{¹⁹F}REDOR (Rotational-Echo Double Resonance) experiments in hydrated lipid bilayers. The obtained REDOR dephasing effects were explained by two components; a short ¹³C/¹⁹F distance (6.9 Å) accounting for 23% of the REDOR dephasing, and a longer one (14 Å) comprising the rest of the dephasing. The shorter distance is likely to reflect the formation of barrel-stave ion channel.

Original language	English
Pages (from-to)	5699-5704
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	19
DOIs	https://doi.org/10.1016/j.bmc.2012.08.016
Publication status	Published - Oct 1 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2012.08.016

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title = "Possible conformation of amphotericin B dimer in membrane-bound assembly as deduced from solid-state NMR",

abstract = "Aiming for structural analysis of amphotericin B (AmB) ion-channel assemblies in membrane, a covalent dimer was synthesized between 13C-labled AmB methyl ester and 19F-labled AmB. The dimer showed slightly weaker but significant biological activities against fungi and red blood cells compared with those of monomeric AmB. Then the dimer was subjected to 13C\{19F\}REDOR (Rotational-Echo Double Resonance) experiments in hydrated lipid bilayers. The obtained REDOR dephasing effects were explained by two components; a short 13C/19F distance (6.9 {\AA}) accounting for 23\% of the REDOR dephasing, and a longer one (14 {\AA}) comprising the rest of the dephasing. The shorter distance is likely to reflect the formation of barrel-stave ion channel.",

author = "Yuichi Umegawa and Takeshi Adachi and Nobuaki Matsumori and Michio Murata",

note = "Funding Information: This work is supported by Grants-in-Aid for Scientific Research (S) (No. 18101010), for Priority Area (A) (No. 16073211) and (B) (No. 17681027) from MEXT, Japan, and in part by JST, ERATO, {\textquoteleft}lipid active structure project.{\textquoteright} ",

year = "2012",

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doi = "10.1016/j.bmc.2012.08.016",

language = "English",

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pages = "5699--5704",

journal = "Bioorganic and Medicinal Chemistry",

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T1 - Possible conformation of amphotericin B dimer in membrane-bound assembly as deduced from solid-state NMR

AU - Umegawa, Yuichi

AU - Adachi, Takeshi

AU - Matsumori, Nobuaki

AU - Murata, Michio

N1 - Funding Information: This work is supported by Grants-in-Aid for Scientific Research (S) (No. 18101010), for Priority Area (A) (No. 16073211) and (B) (No. 17681027) from MEXT, Japan, and in part by JST, ERATO, ‘lipid active structure project.’

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Aiming for structural analysis of amphotericin B (AmB) ion-channel assemblies in membrane, a covalent dimer was synthesized between 13C-labled AmB methyl ester and 19F-labled AmB. The dimer showed slightly weaker but significant biological activities against fungi and red blood cells compared with those of monomeric AmB. Then the dimer was subjected to 13C{19F}REDOR (Rotational-Echo Double Resonance) experiments in hydrated lipid bilayers. The obtained REDOR dephasing effects were explained by two components; a short 13C/19F distance (6.9 Å) accounting for 23% of the REDOR dephasing, and a longer one (14 Å) comprising the rest of the dephasing. The shorter distance is likely to reflect the formation of barrel-stave ion channel.

AB - Aiming for structural analysis of amphotericin B (AmB) ion-channel assemblies in membrane, a covalent dimer was synthesized between 13C-labled AmB methyl ester and 19F-labled AmB. The dimer showed slightly weaker but significant biological activities against fungi and red blood cells compared with those of monomeric AmB. Then the dimer was subjected to 13C{19F}REDOR (Rotational-Echo Double Resonance) experiments in hydrated lipid bilayers. The obtained REDOR dephasing effects were explained by two components; a short 13C/19F distance (6.9 Å) accounting for 23% of the REDOR dephasing, and a longer one (14 Å) comprising the rest of the dephasing. The shorter distance is likely to reflect the formation of barrel-stave ion channel.

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U2 - 10.1016/j.bmc.2012.08.016

DO - 10.1016/j.bmc.2012.08.016

M3 - Article

C2 - 22959766

AN - SCOPUS:84866402146

SN - 0968-0896

VL - 20

SP - 5699

EP - 5704

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 19

ER -

Possible conformation of amphotericin B dimer in membrane-bound assembly as deduced from solid-state NMR

Abstract

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