Differential scanning calorimetry and small angle x-ray diffraction study of the interaction of (R)-PAF, (R)-ET-18-OME and (R)-Lyso-PAF with model membranes.
(R)-PAF, (R)-ET-18-OMe and (R)-Lyso-PAF are ether phospholipid analogs exhibiting different biological activities. All three molecules are highly lipophilic and interact with cell membranes. The manner in which their interactions occur is relevant to their biological activities and may provide information on their mechanism(s) of action at the molecular level. We have studied the interactions of (R)-PAF, (R)-ET-18-OMe and (R)-Lyso-PAF with model membranes using differential scanning calorimetry (DSC). A concentration-dependence study with DSC shows that all three analogs induce similar changes in the thermotropic behavior of model membranes. All produce a slight decrease in the main phase transition temperature of DPPC bilayers (deltaTc = 0.3 to 1.4 degrees C) but have a more substantial effect on the pretransition (deltaTc = 0.8 to 4.5 degrees C). All three disorder phosphatidylcholine (PC) membranes but impart order to PC/cholesterol membranes. We have used small angle x-ray diffraction experiments to supplement the DSC evidence on the topography of the ether lipid analogs in the bilayers. All three appear to insert themselves in the bilayer with their long chain parallel with the membrane bilayer chains.
Xie
X Q
XQ
Institute of Materials Science, School of Pharmacy, University of Connecticut, Storrs 06269, USA.
Moring
J
J
Makriyannis
A
A
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D018836:Inflammation Mediators / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008567:Membranes, Artificial; D010742:Phospholipid Ethers / Q000737:chemistry*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D018836:Inflammation Mediators; D008051:Lipid Bilayers; D008567:Membranes, Artificial; C029271:O-deacetyl platelet activating factor; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C026659:edelfosine; D015060:1,2-Dipalmitoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine