Olivier J L, Chachaty C, Wolf C, Salmon S, Bereziat G
U.A. C.N.R.S. 524, C.H.U. Saint Antoine, Université Paris VI, France.
Biochim Biophys Acta. 1988 Dec 16;963(3):515-24. doi: 10.1016/0005-2760(88)90320-7.
The binding of spin-labeled clofibrate to native and partially delipidated lipoproteins is a rapid, linear and non-saturable process observed up to the critical micellar concentration of the drug. Low-density lipoproteins (LDL) display a lower affinity for the drug than very-low-density lipoproteins (VLDL) and high-density lipoproteins (HDL) relative to their respective specific volume. Unlike various lipophilic drugs, uptake of spin-labeled clofibrate does not correlate with lipoprotein lipid volume. Spin-labeled clofibrate binding to LDL is enhanced when the temperature increases above 25 degrees C. The binding to HDL and VLDL is less temperature-sensitive. The simulation of the ESR spectra has shown that two types of motion should be superimposed for the spin-labeled clofibrate in HDL, in LDL or in partially delipidated LDL. From 40 down to 25 degrees C for HDL and LDL, a fast anisotropic motion is observed. From 25 degrees C down to 5 degrees C, a two-component motion takes place, including a slow isotropic motion of the probe tumbling in a highly hydrophobic environment. Interactions of spin-labeled clofibrate with the apolipoproteins in HDL and LDL are assumed from the emergence of this strongly immobilized component observed when the temperature decreases. In contrast, for spin-labeled clofibrate inserted in the apolar core of VLDL, ESR shows only one component in the whole temperature range (5-40 degrees C). The location of the spin-labeled drug inside the various lipoprotein particles is discussed as a function of temperature.
自旋标记的氯贝丁酯与天然和部分脱脂脂蛋白的结合是一个快速、线性且不饱和的过程，在达到药物的临界胶束浓度之前均可观察到。相对于各自的比容，低密度脂蛋白（LDL）对该药物的亲和力低于极低密度脂蛋白（VLDL）和高密度脂蛋白（HDL）。与各种亲脂性药物不同，自旋标记的氯贝丁酯的摄取与脂蛋白脂质体积无关。当温度升高到25摄氏度以上时，自旋标记的氯贝丁酯与LDL的结合增强。与HDL和VLDL的结合对温度不太敏感。电子自旋共振（ESR）光谱的模拟表明，在HDL、LDL或部分脱脂的LDL中的自旋标记氯贝丁酯应叠加两种类型的运动。对于HDL和LDL，从40摄氏度降至25摄氏度时，观察到快速各向异性运动。从25摄氏度降至5摄氏度时，发生双组分运动，包括探针在高度疏水环境中翻滚的慢速各向同性运动。当温度降低时，从这种强烈固定化组分的出现推测自旋标记的氯贝丁酯与HDL和LDL中的载脂蛋白相互作用。相比之下，对于插入VLDL非极性核心中的自旋标记氯贝丁酯，ESR在整个温度范围（5 - 40摄氏度）仅显示一个组分。根据温度讨论了自旋标记药物在各种脂蛋白颗粒内的位置。
