Ion channel complex of antibiotics as viewed by NMR
Ion channel complex of antibiotics as viewed by NMR
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DOI：
10.1351/pac-con-08-08-37
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发表时间：
2009-06-01
影响因子：
1.8
通讯作者：
Oishi, Tohru
中科院分区：
文献类型：
--
作者：
Murata, Michio;Kasai, Yusuke;Oishi, Tohru
两性霉素B（AmB）通过在真菌膜中形成桶-板条组装体来发挥其药理作用。为了检查AmB与麦角固醇或胆固醇之间的相互作用，制备（13）C-和（19）F-标记的共价缀合物并进行固态NMR测量。使用转子同步双共振实验，如旋转回波双共振（REDOR）和黑索今，我们估计氟原子和其最近的碳在七烯部分之间的距离小于8.6埃，表明麦角甾醇的B环接近AmB多烯部分。构象搜索的AmB-麦角甾醇共轭物使用NMR衍生的限制表明，麦角甾醇分子包围的AmB大会在常规的图像，麦角甾醇插入到AmB分子相反。通过在二肉豆蔻酰磷脂酰胆碱（不含固醇的DMPQ膜）中使用（13）C-和（19）F-标记的AmB来检查AmB-AmB双分子相互作用。在REDOR实验中观察到了头对头和头对尾取向的（13）C-（19）F偶极相互作用。AmB与磷脂酰基链之间的相互作用也被检测到。
Amphotericin B (AmB) exerts its pharmacological effects by forming a barrel-stave assembly in fungal membranes. To examine the interaction between AmB and ergosterol or cholesterol, (13)C- and (19)F-labeled covalent conjugates were prepared and subjected to solid-state NMR measurements. Using rotor-synchronous double-resonance experiments such as rotational echo double resonance (REDOR) and RDX, we estimated the distance between the fluorine atom and its nearest carbon in the heptaene moiety to be less than 8.6 angstrom, indicating that the B ring of ergosterol comes close to the AmB polyene moiety. Conformational search of the AmB-ergosterol conjugate using the NMR-derived constraints suggested that ergosterol molecules surround the AmB assembly in contrast to the conventional image where ergosterol is inserted into AmB molecules. AmB-AmB bimolecular interaction was examined by using (13)C- and (19)F-labeled AmBs in dimyritoylphosphatidylcholine (DMPQ membrane without sterols. (13)C-(19)F dipolar interactions deriving from both head-to-head and head-to-tail orientations were observed in the REDOR experiments. The interactions between AmB and acyl chains of the phospholipid were also detected.