Bioactive Fluorinated Derivative of Amphotericin B.

Matsumori, Nobuaki; Umegawa, Yuichi; Oishi, Tohru; Murata, Michio

doi:10.1002/chin.200547204

Cited by 11 publications

(36 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1D), which is easily detected in NMR measurements, shows almost the same biological activity as unlabelled AmB (Fig. S1 and Table S1), and a method for its efficient preparation from natural products has been established 15 . Using the 19 F centre band-only detection of the exchange (CODEX) method, which is often used to determine the oligomer number of molecules in assemblies 16,17 , we attempted to directly determine the number of AmB molecules per channel assembly (Fig.…”

Section: The Number Of Amb Molecules Constituting One Channel Assemblymentioning

confidence: 87%

“…AmBs fluorinated at positions 14 or 32 and 26,40-13 C2-AmB (Fig. 2C) were prepared by chemical synthesis 15,18 (Supplementary Materials and Methods). Two lipid bilayer models with different lipid compositions and different Erg concentrations in palmitoyloleoylphosphatidylcholine (POPC) were used for 13 C- 19 F rotational echo double resonance (REDOR, Fig.…”

Section: Structural Overview Of Amb Assembly In Membranesmentioning

confidence: 99%

See 1 more Smart Citation

Amphotericin B Assembles into Seven-Molecule Ion Channels in Membrane Domain

Umegawa

Yamamoto²,

Dixit

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Amphotericin B, a long-used antifungal drug, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol, ergosterol. A stable assembly of seven drug molecules was observed to form an ion conductive channel. The structure somewhat resembled the upper half of the barrel-stave model proposed in the 1970s but different substantially in the number of molecules and their arrangement. Based on the structure obtained, the aggregation of the channel assemblies in membranes was investigated and a mechanism was proposed in which complexation with ergosterol stabilizes the drug’s assemblies, leading to their aggregation, and in turn enhancing channel activity. The high-resolution structure is consistent with many previous findings, including structure-activity relationships of the drug, and the channel aggregation provides a more reasonable explanation for the selective toxicity of this drug to fungi.

show abstract

Section: The Number Of Amb Molecules Constituting One Channel Assemblymentioning

confidence: 87%

Section: Structural Overview Of Amb Assembly In Membranesmentioning

confidence: 99%

Amphotericin B Assembles into Seven-Molecule Ion Channels in Membrane Domain

Umegawa

Yamamoto²,

Dixit

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…AmBs fluorinated at positions 14 or 32 and 26,40-13 C2-AmB (Fig. 2C) were prepared by chemical synthesis (15,18) (Supplementary Materials and Methods). Two lipid bilayer models with different lipid compositions and different Erg concentrations in palmitoyloleoylphosphatidylcholine (POPC) were used for 13 C- 19 F rotational echo double resonance (REDOR, Fig.…”

Section: Structural Overview Of Amb Assembly In Membranesmentioning

confidence: 99%

Amphotericin B Assembles into Seven-Molecule Ion Channels: An NMR and Molecular Dynamics Study

Umegawa

Yamamoto²,

Dixit

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of fungal sterol, ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The high-resolution structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects.

show abstract

“…1D), which is easily detected in NMR measurements, shows almost the same biological activity as unlabeled AmB (Fig. S1 and Table S1), and a method for its efficient preparation from natural products has been established (15). Using the 19 F centerband-only detection of the exchange (CODEX) method, which is often used to determine the oligomer number of molecules in assemblies (16,17), we attempted to directly determine the number of AmB molecules per channel assembly (Fig.…”

Section: How Many Amb Molecules Constitute One Channel Assemblymentioning

confidence: 99%