title: Membrane permeabilizing activity of amphotericin B is affected by chain length of phosphatidylcholine added as minor constituent.
abstract: The effect of acyl-chain length of phospholipid on the membrane permeabilizing activity of amphotericin B (AmB) was examined using egg phosphatidylcholine (eggPC) liposomes containing 5% or 20% phosphatidylcholine with various lengths of fatty acyl chains from C(10) to C(18); 1,2-dicapryloyl-sn-glycero-3-phosphocholine (DCPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The membrane activity of AmB was evaluated by two methods; the drug was added to a liposome suspension (added-via-aqua), or mixed with lipids prior to liposome preparation (mixed-with-lipid). In both cases, K(+) influx by AmB was measured as pH change inside liposomes by 31P-NMR. The C(10) and C(12) acyl phospholipids markedly enhanced the activity of AmB, the C(14) and C(16) lipids virtually showed no effect, and the C(18) lipid was inhibitory to the AmB's action. Clear distinction between the C(12) and C(14) lipids, which differ only in acyl chains by two carbons, implies that molecular interaction between phospholipid and AmB is partly due to the matching of their hydrophobic length.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-16 Machikaneyama, Toyonaka, 560-0043 Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Michio
authors.initials: M
authors.lastname: Murata
mesh_terms: D000215:Acylation; D000666:Amphotericin B / Q000737:chemistry*; D007473:Ion Channels / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D046911:Macromolecular Substances; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D008968:Molecular Conformation; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry*; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D007473:Ion Channels; D008081:Liposomes; D046911:Macromolecular Substances; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D012996:Solutions; D000666:Amphotericin B