Abstract
Small unilamellar vesicles (SUV) composed of zwitterionic phosphatidylcholine and two different anionic phospholipids, phosphatidic acid and phosphatidylserine, in different compositions, were employed to study the membrane interaction of an antitumor antibiotic, mithramycin (MTR). Binding of MTR to dimyristoylphosphatidylcholine (DMPC) liposomes containing the anionic phospholipid dimyristoylphosphatidic acid (DMPA) was estimated by measuring the increase in intensity of the intrinsic fluorescence of MTR with increasing concentrations of phospholipids. Membrane perturbations were observed in acidic SUV of DMPC/DMPA and DMPC/bovine brain phosphatidylserine by MTR and its magnesium complex as studied by monitoring the leakage of the entrapped fluorescent marker carboxyfluorescein and by electron microscopic measurements of the size of the liposomes. These results indicated a possible role of anionic phospholipids in mediating binding of MTR and its magnesium complex to the cell surface membranes before reaching the target DNA.
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