A synthetic approach to the channel complex structure of antibiotic in a membrane

Backbone 19 F-labeled amphotericin B for solidstate NMR analysis

Hiroshi Tsuchikawa, Yuichi Umegawa, Michio Murata, Tohru Oishi

Research output: Contribution to journalArticle

Abstract

Over 40 years have passed since a well-known hypothesis of a channel-like amphotericin B (AmB) assembly with ergosterol (Erg) was proposed as the mode of action accounting for its selective fungal toxicity. However, no reliable or direct experimental evidence had been obtained until recently mainly because of significant difficulties in structural analysis of the self-assembly of small molecules specifically formed inside a membrane. In this study, we describe the accomplishments in the chemical synthesis of two AmB derivatives with fluorine labeling in the molecular skeleton for applying solid-state NMR techniques. The interatomic distance measurements using these chemically prepared probes have successfully shown the detailed AmB-Erg bimolecular interaction in the channel structure for the first time. The latest solid-state NMR analysis backed by synthetic chemistry is expected to achieve a breakthrough in elucidating the long-unsolved AmB channel architecture.

Original languageEnglish
Pages (from-to)1197-1205
Number of pages9
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume76
Issue number11
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Amphotericin B
Nuclear magnetic resonance
Anti-Bacterial Agents
Membranes
Ergosterol
Distance measurement
Fluorine
Structural analysis
Self assembly
Labeling
Toxicity
Derivatives
Molecules

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

A synthetic approach to the channel complex structure of antibiotic in a membrane : Backbone 19 F-labeled amphotericin B for solidstate NMR analysis. / Tsuchikawa, Hiroshi; Umegawa, Yuichi; Murata, Michio; Oishi, Tohru.

In: Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, Vol. 76, No. 11, 01.01.2018, p. 1197-1205.

Research output: Contribution to journalArticle

@article{520b9e3f45bb43a78938ecc48f602622,
title = "A synthetic approach to the channel complex structure of antibiotic in a membrane: Backbone 19 F-labeled amphotericin B for solidstate NMR analysis",
abstract = "Over 40 years have passed since a well-known hypothesis of a channel-like amphotericin B (AmB) assembly with ergosterol (Erg) was proposed as the mode of action accounting for its selective fungal toxicity. However, no reliable or direct experimental evidence had been obtained until recently mainly because of significant difficulties in structural analysis of the self-assembly of small molecules specifically formed inside a membrane. In this study, we describe the accomplishments in the chemical synthesis of two AmB derivatives with fluorine labeling in the molecular skeleton for applying solid-state NMR techniques. The interatomic distance measurements using these chemically prepared probes have successfully shown the detailed AmB-Erg bimolecular interaction in the channel structure for the first time. The latest solid-state NMR analysis backed by synthetic chemistry is expected to achieve a breakthrough in elucidating the long-unsolved AmB channel architecture.",
author = "Hiroshi Tsuchikawa and Yuichi Umegawa and Michio Murata and Tohru Oishi",
year = "2018",
month = "1",
day = "1",
doi = "10.5059/yukigoseikyokaishi.76.1197",
language = "English",
volume = "76",
pages = "1197--1205",
journal = "Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry",
issn = "0037-9980",
publisher = "社団法人 有機合成化学協会",
number = "11",

}

TY - JOUR

T1 - A synthetic approach to the channel complex structure of antibiotic in a membrane

T2 - Backbone 19 F-labeled amphotericin B for solidstate NMR analysis

AU - Tsuchikawa, Hiroshi

AU - Umegawa, Yuichi

AU - Murata, Michio

AU - Oishi, Tohru

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Over 40 years have passed since a well-known hypothesis of a channel-like amphotericin B (AmB) assembly with ergosterol (Erg) was proposed as the mode of action accounting for its selective fungal toxicity. However, no reliable or direct experimental evidence had been obtained until recently mainly because of significant difficulties in structural analysis of the self-assembly of small molecules specifically formed inside a membrane. In this study, we describe the accomplishments in the chemical synthesis of two AmB derivatives with fluorine labeling in the molecular skeleton for applying solid-state NMR techniques. The interatomic distance measurements using these chemically prepared probes have successfully shown the detailed AmB-Erg bimolecular interaction in the channel structure for the first time. The latest solid-state NMR analysis backed by synthetic chemistry is expected to achieve a breakthrough in elucidating the long-unsolved AmB channel architecture.

AB - Over 40 years have passed since a well-known hypothesis of a channel-like amphotericin B (AmB) assembly with ergosterol (Erg) was proposed as the mode of action accounting for its selective fungal toxicity. However, no reliable or direct experimental evidence had been obtained until recently mainly because of significant difficulties in structural analysis of the self-assembly of small molecules specifically formed inside a membrane. In this study, we describe the accomplishments in the chemical synthesis of two AmB derivatives with fluorine labeling in the molecular skeleton for applying solid-state NMR techniques. The interatomic distance measurements using these chemically prepared probes have successfully shown the detailed AmB-Erg bimolecular interaction in the channel structure for the first time. The latest solid-state NMR analysis backed by synthetic chemistry is expected to achieve a breakthrough in elucidating the long-unsolved AmB channel architecture.

UR - http://www.scopus.com/inward/record.url?scp=85056325921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056325921&partnerID=8YFLogxK

U2 - 10.5059/yukigoseikyokaishi.76.1197

DO - 10.5059/yukigoseikyokaishi.76.1197

M3 - Article

VL - 76

SP - 1197

EP - 1205

JO - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry

JF - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry

SN - 0037-9980

IS - 11

ER -