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.