Membrane interaction of amphotericin B as single-length assembly examined by solid state NMR for uniformly 13C-enriched agent |
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Authors: | Matsuoka Shigeru Ikeuchi Hiroki Umegawa Yuichi Matsumori Nobuaki Murata Michio |
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Institution: | Department of Chemistry, Graduate School of Science, Osaka University, 1-16 Machikaneyama, Toyonaka, Osaka 560-0043, Japan. |
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Abstract: | The membrane interaction of amphotericin B (AmB), one of the most important anti-fungal drugs, was investigated by solid state NMR measurements of uniformly 13C-enriched AmB, which was prepared by the culture of the drug-producing microorganism in the presence of u-13C6]glucose. All the 13C NMR signals of AmB upon binding to DLPC membrane were successfully assigned on the basis of the 13C-13C correlation spectrum. 13C-31P RDX (Rotational-Echo Double Resonance for X-clusters) experiments clearly revealed the REDOR dephasing effects for carbon atoms residing in the both terminal parts, whereas no dephasing was observed for the middle parts including polyolefinic C20-C33 and hydroxyl-bearing C8/C9 parts. These observations suggest that AmB binds to DLPC membrane with a high affinity to the phospholipid and spans the membrane with a single molecular length. |
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