Membrane interaction of amphotericin B as single-length assembly examined by solid state NMR for uniformly 13C-enriched agent.
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.
Matsuoka
Shigeru
S
Department of Chemistry, Graduate School of Science, Osaka University, 1-16 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Ikeuchi
Hiroki
H
Umegawa
Yuichi
Y
Matsumori
Nobuaki
N
Murata
Michio
M
D000666:Amphotericin B / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002247:Carbon Isotopes; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry / Q000187:drug effects
D000935:Antifungal Agents; D002247:Carbon Isotopes; D007202:Indicators and Reagents; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; C015153:1,2-dilauroylphosphatidylcholine; D000666:Amphotericin B