Emiko Okamura - "Drug Binding and Mobility Relating to the Thermal Fluctuation in Fluid Lipid Membranes" E.Okamura and N.Yoshii, J. Chem. Phys., 129, 215102 (2008).

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  "Drug Binding and Mobility Relating to the Thermal Fluctuation in   Fluid Lipid Membranes" E.Okamura and N.Yoshii, J. Chem.   Phys., 129, 215102 (2008).


  Drug  binding  and mobility   influid lipid   bilayer membranes are  quantified  in situ  by using the   multinuclear solution   NMR combined  with the   pulsed-field-gradient   technique. One-dimensional   and pulsed-field-gradient   19F and 1H NMR signals of an anticancer   drug, 5-fluorouracil (5FU) are analyzed at   283-313 K in the presence of large unilamellar   vesicles (LUV) of egg   phosphatidylcholine  (EPC) as model cell membranes.  The   simultaneous   observation of the   membrane-bound and free 5FU  signals enables   to quantify in what amount of 5FU  is bound to the   membrane and how fast 5FU   is moving within the membrane in relation to the thermal   fluctuation of the soft, fluid environment. It is shown that the   mobility ofmembrane-bound  5FU is slowed   down by almost two orders of magnitude and similar to the lipid   movement in the membrane, the movement closely related to the   intra-membrane fluidity. The mobility of 5FU and EPC is,   however, not similar at 313 K; the 5FU movement is enhanced in   the membrane as a result ofthe loose binding   of 5FU in  the  lipid   matrices. The   membrane-bound fraction of 5FU is ~0.1 and   almost unaltered over the temperature range examined. It is also   independent of the  5FU  concentration   from 2 to 30 mM with respect to   the 40-50 mM LUV. The free energy   of the 5FU  binding is   estimated at -4~-2   kJ/mol, the magnitude   always close to the thermal   fluctuation, 2.4~2.6 kJ/mol.

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