Interactions of aminoglycoside antibiotics with phospholipids. A deuterium nuclear magnetic resonance study.
The effect of several aminoglycoside (AG) antibiotics on aqueous multilamellar dispersions of mixtures of phosphatidylinositol (PI) and deuterated phosphatidylcholine (PC) has been studied by deuterium (2H) NMR. Isepamicin and amikacin gave rise to no significant changes in 2H-NMR lineshape relative to that of the lipid mixture without antibiotic. Both kanamycin A and B, which have a greater affinity for PI than the other two antibiotics examined in this study, induced temperature-dependent changes in 2H-NMR lineshapes and associated spectral moments. The results are consistent with an antibiotic-induced lateral phase separation giving rise to PC-enriched domains free of drug and PI-AG domains. These effects are correlated with the inhibitory potency of aminoglycosides towards PC degradation.
Schanck
A
A
Laboratoire de Chimie-Physique et de Cristallographie and Research Center for Advanced Materials, Université Catholique de Louvain, Belgium.
Mingeot-Leclercq
M P
MP
Tulkens
P M
PM
Carrier
D
D
Smith
I C
IC
Jarrell
H C
HC
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D002240:Carbohydrate Sequence; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry; D010716:Phosphatidylinositols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine