从固态 NMR 推断出两性霉素 B 二聚体在膜结合组装中的可能构象。
Possible conformation of amphotericin B dimer in membrane-bound assembly as deduced from solid-state NMR.
机构信息
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
出版信息
Bioorg Med Chem. 2012 Oct 1;20(19):5699-704. doi: 10.1016/j.bmc.2012.08.016. Epub 2012 Aug 19.
Aiming for structural analysis of amphotericin B (AmB) ion-channel assemblies in membrane, a covalent dimer was synthesized between (13)C-labled AmB methyl ester and (19)F-labled AmB. The dimer showed slightly weaker but significant biological activities against fungi and red blood cells compared with those of monomeric AmB. Then the dimer was subjected to (13)C{(19)F}REDOR (Rotational-Echo Double Resonance) experiments in hydrated lipid bilayers. The obtained REDOR dephasing effects were explained by two components; a short (13)C/(19)F distance (6.9Å) accounting for 23% of the REDOR dephasing, and a longer one (14Å) comprising the rest of the dephasing. The shorter distance is likely to reflect the formation of barrel-stave ion channel.
为了对两性霉素 B（AmB）离子通道在膜中的结构进行分析，合成了（13）C 标记的 AmB 甲酯和（19）F 标记的 AmB 的共价二聚体。与单体 AmB 相比，二聚体对真菌和红细胞的活性略有减弱，但仍具有显著的生物学活性。然后，将二聚体在水合脂质双层中进行（13）C{(19)F}REDOR（旋转回波双共振）实验。通过两个分量解释了获得的 REDOR 去相位效应；一个较短的（13）C/（19）F 距离（6.9Å）占 REDOR 去相位的 23%，一个较长的距离（14Å）占去相位的其余部分。较短的距离可能反映了桶状-棒状离子通道的形成。
Zotero 插件