Chirality of the interaction of mithramycin with phosphatidylcholine-bilayer membranes in the presence of Mg2+ or Zn2+.
Binding of the antitumor compound mithramycin to dipalmitoyl-sn-glycerophosphocholine and dimyristoyl-sn-glycerophosphocholine (Myr2GroPCho) model membrane (small unilamellar vesicles, SUV) bilayers was shown to be dependent on the molecular packing of the lipids and on the presence of Zn2+ or Mg2+. The CD properties of mithramycin have been used to follow its complexation to Zn2+ and to Mg2+. In the absence of SUV, Mg2+ and Zn2+ are each able to form with mithramycin two types of complexes of different chirality: at low molar ratios of M2+ to mithramycin, a complex in the left-handed conformation is obtained whereas at high molar ratios the complex formed has the right-handed conformation. In the presence of Zn2+ or Mg2+, mithramycin binds to SUV in the gel-phase state as a dimer in the left-handed conformation. No binding is observed when SUV are in liquid-crystal state.
Demicheli
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Laboratoire de Chimie Bioinorganique, Université Paris Nord, Bobigny, France.
Garnier-Suillerot
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D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism*; D008926:Plicamycin / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013696:Temperature; D015032:Zinc / Q000378:metabolism*
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C039559:1,3-dipalmitoyl-2-phosphatidylcholine; D008274:Magnesium; D015032:Zinc; D008926:Plicamycin