Speelmans G, Sips W H, Grisel R J, Staffhorst R W, Fichtinger-Schepman A M, Reedijk J, de Kruijff B
Department of Biochemistry of Membranes, University of Utrecht, The Netherlands.
Biochim Biophys Acta. 1996 Aug 14;1283(1):60-6. doi: 10.1016/0005-2736(96)00080-6.
The interaction of the anti-cancer drug cis-diamminedichloroplatinum(II) (cisPt) with model membranes was studied, with emphasis on the cisPt and phospholipid species involved. Binding studies using large unilamellar vesicles have revealed that: (i) Interaction involved negatively charged phospholipids only, and (ii) Interaction with negatively charged phospholipids was observed only in buffers with low Cl- concentration, indicating that aquated, positively charged cisPt is involved. Binding to all negatively charged phospholipids tested was highest at pH 6.0. At pH 7.4 a high and specific binding was observed with phosphatidic acid and phosphatidylserine. The consequences of cisPt binding on the organization of lipids was investigated with differential scanning calorimetry studies. These studies have indicated a higher ordering of dispersions of negatively charged phospholipids in the presence of divalent cationic cisPt. Summarizing, the interaction of positively charged cisPt species with negatively charged phospholipids is significant and should be considered in in vivo experiments.
研究了抗癌药物顺二氯二氨铂（II）（cisPt）与模型膜的相互作用，重点关注所涉及的cisPt和磷脂种类。使用大单层囊泡的结合研究表明：（i）相互作用仅涉及带负电荷的磷脂，并且（ii）仅在低Cl-浓度的缓冲液中观察到与带负电荷的磷脂的相互作用，表明涉及水合的带正电荷的cisPt。在pH 6.0时，与所有测试的带负电荷的磷脂的结合最高。在pH 7.4时，观察到与磷脂酸和磷脂酰丝氨酸有高特异性结合。用差示扫描量热法研究了cisPt结合对脂质组织的影响。这些研究表明，在二价阳离子cisPt存在下，带负电荷的磷脂分散体的有序性更高。总之，带正电荷的cisPt种类与带负电荷的磷脂之间的相互作用很显著，在体内实验中应予以考虑。
