Srivastava S, Phadke R S, Govil G
Tata Institute of Fundamental Research, Bombay, India.
Mol Cell Biochem. 1989;91(1-2):99-109. doi: 10.1007/BF00228084.
The characteristics of vesicles formed from Dipalmitoyl Phosphatidyl Choline (DPPC) are sensitive to the presence of perturbing molecules such as drugs, peptides, hormones and vitamins. We have used ESR spin labeling and NMR techniques for studying interaction of such molecules with lipid bilayers. ESR spin labeling has been used to monitor thermotropic behaviour of model membranes. Different NMR probes such as 1H, 31P, 13C have been used to gather information regarding the mode of interaction. It has been observed that the model membrane systems respond differently depending upon the localization of the perturbing molecules in the lipid bilayer. Small molecules such as neurotransmitters epinephrine and norepinephrine decrease gel to liquid crystalline phase transition temperature significantly even when present in small amounts. Vitamin E acetate having a hydrophobic hydrocarbon tail orients parallel to the lipid molecule and thereby exhibits dynamics similar to palmitate chain. When the acetate group is replaced by hydroxyl group (alpha-tocopherol), the phase transition becomes broad and the lipid molecules loose freedom of lateral diffusion. This can be attributed to formation of hydrogen bond between the hydroxyl group of alpha-tocopherol and phosphate moiety of lipid. The conformation of antidepressants nitroxazepine and imipramine is significantly altered when embedded in lipid bilayer. Anaesthetic etomidate not only modifies thermotropic characteristics but also induces polymorphism. The normal bilayer arrangement of lipids gets transformed into hexagonal packing. Amino acid tryptophan induces cubic phases in the normal bilayer arrangement of DPPC dispersions. Peptide gonadoliberin shows a reduced internal motion due to the lipid peptide interaction. The major consequences of binding of lipids with externally added molecules are changes in the fluidity and permeability properties of membranes. It has been shown that permeability is effected by the presence of molecules such as propranolol, alpha-tocopherol and its analogue, neurotransmitters, etc. The magnetic resonance methods have thus evolved as power techniques in the study of membrane structure and function.
由二棕榈酰磷脂酰胆碱（DPPC）形成的囊泡的特性对诸如药物、肽、激素和维生素等干扰分子的存在很敏感。我们已使用电子自旋共振（ESR）自旋标记和核磁共振（NMR）技术来研究此类分子与脂质双层的相互作用。ESR自旋标记已用于监测模型膜的热致行为。不同的NMR探针，如1H、31P、13C，已被用于收集有关相互作用模式的信息。据观察，模型膜系统根据干扰分子在脂质双层中的定位而有不同反应。诸如神经递质肾上腺素和去甲肾上腺素等小分子即使少量存在也会显著降低凝胶到液晶相的转变温度。具有疏水烃尾的维生素E醋酸酯与脂质分子平行取向，从而表现出与棕榈酸酯链相似的动力学。当醋酸酯基团被羟基取代（α-生育酚）时，相变变宽，脂质分子失去横向扩散的自由度。这可归因于α-生育酚的羟基与脂质的磷酸部分之间形成氢键。抗抑郁药硝西泮和丙咪嗪嵌入脂质双层时构象会显著改变。麻醉药依托咪酯不仅改变热致特性，还会诱导多态性。脂质的正常双层排列转变为六方堆积。氨基酸色氨酸在DPPC分散体的正常双层排列中诱导立方相。肽促性腺激素释放激素由于脂质-肽相互作用而内部运动减少。脂质与外部添加分子结合的主要后果是膜的流动性和通透性特性发生变化。已表明，诸如普萘洛尔、α-生育酚及其类似物、神经递质等分子的存在会影响通透性。因此，磁共振方法已发展成为研究膜结构和功能的有力技术。
