Effects of cyclosporin A on model lipid membranes

被引:26
作者
Lambros, MP [1 ]
Rahman, YE
机构
[1] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA
[2] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA
关键词
immunosuppressant; cyclosporin A; small-angle X-ray diffraction;
D O I
10.1016/j.chemphyslip.2004.04.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclosporin A (CSA) is a widely used immunosuppressant drug for transplant therapy, however its limitation is its toxicity. The effect of CSA on model membranes such as dimyristoyl phosphatidylcholine (DMPC) bilayers was studied using small-angle X-ray diffraction and differential scanning calorimetry (DSC). CSA abolishes the pretransition and affects the transition of DMPC model membranes in a concentration-related manner as is shown by DSC. CSA induces a second peak at the high temperature side of the main transition, which is interpreted as a phase separation between areas rich and poor in CSA concentration. Small angle X-ray diffraction shows that the repeat distance of the DMPC bilayers in the lamellar Lalpha state increases as a function of concentration up to 10 mol% and remains constant thereafter. Furthermore, CSA affects the fatty acyl chains of the bilayer, especially the part of the chain proximal to the head group. In conclusion, CSA, as both small-angle X-ray diffraction and DSC show, affects in a concentration-wise manner the DMPC model membranes and perturbs the bilayer, in particular the acyl chain region. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:63 / 69
页数:7
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