Document 0554
 DOCN  M9440554
 TI    Membrane properties of antiviral phospholipids containing heteroatoms in
       the acyl chains.
 DT    9404
 AU    Qiu X; Pidgeon C; Department of Medicinal Chemistry and Pharmacognosy,
       School of; Pharmacy, Purdue University, West Lafayette, Indiana 47907.
 SO    Biochemistry. 1994 Feb 1;33(4):960-72. Unique Identifier : AIDSLINE
       MED/94137726
 AB    Phospholipids containing heteroatoms in the lipid acyl chains, e.g.,
       1,2-bis(12-methoxydodecanoyl)-sn-3-phosphocholine (L-AC2), exhibit
       potent anti-HIV activity [Pidgeon, C., Markovich, R. J., Liu, M. D.,
       Holzer, T., Novak, R., & Keyer, K. (1993) J. Biol. Chem. 268,
       7773-7778]. AC2 is a synthetic chemical analog of the long-chain
       phospholipid, dimyristoylphosphatidylcholine (DMPC). Sonicated AC2 lipid
       dispersions would not entrap either Dextran-4000 or Mn2+ used as aqueous
       space markers. The lack of entrapment of aqueous space markers indicates
       that the AC2 structures do not contain an aqueous core that is the
       characteristic morphology of conventional lipid vesicles formed by
       sonication. Transmission electron microscopy (TEM) showed that sonicated
       AC2 lipid dispersions are small homogeneous particles approximately
       70-100 A in diameter. 1H NMR experiments using Mn2+ as a broadening
       reagent indicated that Mn2+ was accessible to all of the AC2
       phospholipid headgroups in the AC2 lipid particles formed by sonication.
       The temperature dependence of 1H spin-lattice (T1) relaxation time
       measurements revealed that the motional activation energies increased
       from the choline headgroup to the end of the acyl chains of AC2
       molecules in the AC2 lipid particles formed by sonication. Collectively
       these results demonstrate that AC2 forms micelles. NOESY experiments
       showed that the AC2 molecules forming the micelle structures have
       hindered motion compared to conventional short-chain phosphatidylcholine
       micelles. 31P NMR spectroscopy and TEM showed that the AC2 micelles
       extensively fuse into giant bilayer liposomes (single-layered) when the
       temperature is reduced from above to below the main phase transition
       temperature of AC2. This micelle-to-liposome transition is an
       irreversible process; increasing the temperature above the Tm does not
       cause the formation of micelles. Thus, a main finding is that AC2
       micelles formed by sonication are not thermodynamically stable because
       they fuse into large unilamellar vesicles that are stable to further
       changes in temperature. These unusual membrane properties of sonicated
       AC2 dispersions may be important for the antiviral activity and
       metabolism of the phospholipids.
 DE    Antiviral Agents/CHEMISTRY/*PHARMACOLOGY  Cell Membrane/DRUG EFFECTS
       Dimyristoylphosphatidylcholine/*ANALOGS & DERIVATIVES/CHEMISTRY/
       METABOLISM/*PHARMACOLOGY  Liposomes  Micelles  Microscopy, Electron
       Nuclear Magnetic Resonance  Support, U.S. Gov't, Non-P.H.S.  Support,
       U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).