Membrane interaction of amphotericin B as single-length assembly examined by solid state NMR for uniformly 13C-enriched agent

Bioorg Med Chem. 2006 Oct 1;14(19):6608-14. doi: 10.1016/j.bmc.2006.06.001. Epub 2006 Jun 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / chemistry*
  • Amphotericin B / isolation & purification
  • Amphotericin B / pharmacology*
  • Antifungal Agents / chemistry*
  • Antifungal Agents / isolation & purification
  • Antifungal Agents / pharmacology*
  • Carbon Isotopes
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Membranes, Artificial
  • Phosphatidylcholines / chemistry
  • Streptomyces / chemistry
  • Streptomyces / drug effects

Substances

  • Antifungal Agents
  • Carbon Isotopes
  • Indicators and Reagents
  • Membranes, Artificial
  • Phosphatidylcholines
  • 1,2-dilauroylphosphatidylcholine
  • Amphotericin B