Molecular dynamics of antitumor ether-linked phospholipids in model membranes: a spin-label study.
We have synthesized a spin-labeled derivative of ET-18-OCH3, a known antitumor ether-linked phospholipid. The spin-labeled analog was shown to be as potent as ET-18-OCH3 in inhibiting 3H-thymidine uptake of HL60 leukemic cells. Electron spin resonance (ESR) studies showed that the mobility of this ether-linked phospholipid in the membrane is more restricted when compared to its ester-linked counterparts. It is probable that the absence of the bulky carbonyl oxygens allows closer packing of the two alkyl chains in the ether-linked phospholipid, thereby reducing the angular amplitude of the motion of the alkyl chains. These findings may be of importance in elucidating mechanisms by which the antitumor ether-linked phospholipids perturb the structure of cellular membranes.
Lai
C S
CS
Department of Radiology, Medical College of Wisconsin, Milwaukee 53226.
Joseph
J
J
Shih
C C
CC
D015060:1,2-Dipalmitoylphosphatidylcholine; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D015394:Molecular Structure; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D013113:Spin Labels; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008081:Liposomes; D010742:Phospholipid Ethers; D013113:Spin Labels; C026659:edelfosine; D015060:1,2-Dipalmitoylphosphatidylcholine; D004247:DNA