Drug binding and mobility relating to the thermal fluctuation in fluid lipid membranes.
Drug binding and mobility relating to the thermal fluctuation in fluid lipid membranes.
复制标题
与流体脂质膜的热波动相关的药物结合和迁移率。
DOI：
10.1063/1.3023035
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
N. Yoshii
中科院分区：
文献类型：
--
作者：
E. Okamura;N. Yoshii
利用多核核磁共振结合脉冲场梯度技术，对流体脂质双层膜中的药物结合和流动性进行了原位定量研究。在283-313 K温度范围内，以卵磷脂（EPC）的大单层囊泡（LUV）为模型细胞膜，分析了抗癌药物5-氟尿嘧啶（5-FU）的一维和脉冲场梯度（19）F和（1）H NMR信号。膜结合和游离5 FU信号的同时观察使得能够定量与膜结合的5 FU的量以及5 FU在膜内相对于软流体环境的热波动移动的速度。结果表明，膜结合的5 FU的流动性减慢了近两个数量级，类似于膜中的脂质运动，该运动与膜内流动性密切相关。然而，5 FU和EPC的迁移率在313 K时并不相似;由于5 FU在脂质基质中的松散结合，5 FU移动在膜中增强。5 FU的膜结合分数约为0.1，在检查的温度范围内几乎不变。相对于40-50 mM LUV，它也不依赖于2 - 30 mM的5 FU浓度。5 FU结合的自由能估计为-4至-2 kJ/mol，大小总是接近热波动，2.4-2.6 kJ/mol。
Drug binding and mobility in fluid lipid bilayer membranes are quantified in situ by using the multinuclear solution NMR combined with the pulsed-field-gradient technique. One-dimensional and pulsed-field-gradient (19)F and (1)H NMR signals of an anticancer drug, 5-fluorouracil (5FU) are analyzed at 283-313 K in the presence of large unilamellar vesicles (LUVs) of egg phosphatidylcholine (EPC) as model cell membranes. The simultaneous observation of the membrane-bound and free 5FU signals enables to quantify in what amount of 5FU is bound to the membrane and how fast 5FU is moving within the membrane in relation to the thermal fluctuation of the soft, fluid environment. It is shown that the mobility of membrane-bound 5FU is slowed down by almost two orders of magnitude and similar to the lipid movement in the membrane, the movement closely related to the intramembrane fluidity. The mobility of 5FU and EPC is, however, not similar at 313 K; the 5FU movement is enhanced in the membrane as a result of the loose binding of 5FU in the lipid matrices. The membrane-bound fraction of 5FU is approximately 0.1 and almost unaltered over the temperature range examined. It is also independent of the 5FU concentration from 2 to 30 mM with respect to the 40-50 mM LUV. The free energy of the 5FU binding is estimated at -4 to -2 kJ/mol, the magnitude always close to the thermal fluctuation, 2.4-2.6 kJ/mol.
影响因子：
3.4
作者：
Pickholz, M;Saiz, L;Klein, ML
通讯作者：
Klein, ML