Neigh G S, Ananthanarayanan V S
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
Biochem Mol Biol Int. 1996 May;39(1):53-61. doi: 10.1080/15216549600201051.
We have characterized the binding of Ca2+ and Mg2+ to the anti-inflammatory drug diflunisal in acetonitrile and demonstrated the drug-mediated transport of Ca2+ across the lipid bilayer in unilamellar vesicles made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Fluorescence and difference absorption spectral data show that diflunisal undergoes a significant conformational change on binding Ca2+ and Mg2+ forming, respectively, 1:2 and 1:1 cation:drug complexes with Kd in the low microM range. The kinetics of transport showed that Ca2+ was transported into the vesicle as 1:2 Ca2+:diflunisal sandwich complex. This suggests that the interaction of the drug with the cation in the lipid-mimetic solvent are similar. The biological relevance of the Ca(2+)-binding and translocating abilities of diflunisal is examined in light of the reported ionophoretic properties of several phospholipids as well as cyclooxygenase and lipoxygenase products.
我们已对钙离子和镁离子与抗炎药双氟尼酸在乙腈中的结合进行了表征，并证明了该药物介导的钙离子在由1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱制成的单层囊泡中跨脂质双层的运输。荧光和差示吸收光谱数据表明，双氟尼酸在结合钙离子和镁离子时分别经历了显著的构象变化，形成了阳离子与药物的1:2和1:1复合物，解离常数在低微摩尔范围内。运输动力学表明，钙离子以1:2的钙离子：双氟尼酸夹心复合物形式运输到囊泡中。这表明该药物在类脂溶剂中与阳离子的相互作用是相似的。鉴于几种磷脂以及环氧化酶和脂氧合酶产物已报道的离子载体特性，我们研究了双氟尼酸结合和转运钙离子能力的生物学相关性。
