Title:Spectroscopic Studies on the Interaction of Mefloquine with Phosphatidylcholine- Phosphatidylserine Bilayer Vesicle and Bovine Serum Albumin
VOLUME: 8 ISSUE: 3
Author(s):Shigehiko Takegami, Arika Otani, Yoko Otake and Tatsuya Kitade
Affiliation:Department of Analytical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchicho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Keywords:Binding constant, Bovine serum albumin, Fluorescence quenching, 19F nuclear magnetic resonance, Liposome,
Mefloquine, Partition coefficient, Phosphatidylcholine, Phosphatidylserine, Second-derivative spectrophotometry, Zeta potential
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.
