Abstract
To assess the interaction of mefloquine (MQ) with biomembranes and serum albumin, the partitioning of MQ into phosphatidylcholine-phosphatidylserine small unilamellar vesicles (PC-PS SUV) and its binding with bovine serum albumin (BSA) were examined using various spectroscopic methods. The partition coefficients (Kps) of MQ, determined by the second-derivative spectrophotometric method, increased in accordance with the PS content in PC-PS SUV: the Kp values for PC-PS SUV with PS contents of 10 mol% were about 2.5 times that for PC SUV. The zeta potential values of PC-PS SUV fell from -10 mV at a PS content of 0 mol% to -42 mV at PS contents of 10 mol%, and were found to depend to some extent on the Kp values. Meanwhile, the binding constant (logK) and the number of binding sites (n) for the binding of MQ to BSA were determined using a fluorescence quenching method. These values were significantly reduced by the presence of Cl– ions, from 5.55 to 4.66 for logK and from 1.30 to 1.11 for n. To examine the binding site of MQ on BSA, a 19F nuclear magnetic resonance (NMR) spectroscopic study was performed using typical competing ligands bound to BSA. The results revealed that whereas most of the MQ binds nonspecifically to BSA, MQ also partially binds to Site II. Finally, these results showed that the major interactions between MQ and PC-PS SUV or BSA were essentially different; the partitioning of MQ into PC-PS SUV was electrostatic and the binding of MQ to BSA was hydrophobic.
Keywords: Binding constant, Bovine serum albumin, Fluorescence quenching, 19F nuclear magnetic resonance, Liposome, Mefloquine, Partition coefficient, Phosphatidylcholine, Phosphatidylserine, Second-derivative spectrophotometry, Zeta potential
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