Deuterium NMR investigation of an amphotericin B derivative in mechanically aligned lipid bilayers.
The methyl-d(3) amide derivative of the polyene antibiotic amphotericin B was synthesized, assayed for biological activity, incorporated into mechanically aligned bilayers of dipalmitoylphosphatidylcholine (DPPC), and examined by deuterium and phosphorus NMR. The amide derivative has a lesser, but qualitatively similar, biological activity relative to amphotericin B. Incorporation of the amide derivative and ergosterol into aligned DPPC bilayers resulted in a single, stable bilayer phase, as shown by phosphorus NMR of the DPPC headgroups. Deuterium NMR spectra revealed one major (2)H quadrupolar splitting and one major (2)H-(1)H dipolar splitting in the liquid-crystalline phase, consistent with a high degree of alignment and a single, averaged physical state for amphotericin B methyl-d(3) amide in the bilayer. Variations of the quadrupolar and dipolar splittings as a function of macroscopic sample orientation and temperature indicated that the amide derivative undergoes fast rotation about a motional axis that is parallel to the bilayer normal.
Hing
A W
AW
Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
Schaefer
J
J
Kobayashi
G S
GS
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000737:chemistry*; D003903:Deuterium; D004875:Ergosterol / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013816:Thermodynamics
D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; D000666:Amphotericin B; D003903:Deuterium; D004875:Ergosterol