Chemical Synthesis and Mass Spectrometry of PAF

  • Robert C. Murphy
  • Keith L. Clay


Elucidation of the exact chemical structure of a biologically active molecule often presents a milestone in the search for understanding of the physiological or pathophysiological role such a molecule may play in biology. While the initial description of the biological activity of a substance provides the necessary interest to focus further investigations, the knowledge of the covalent structure of the substance permits, for the first time, chemical synthesis of quantities of pure material for detailed pharmacological studies, notwithstanding the proof of the identity of the biological substance. Furthermore, the knowledge of the covalent structure permits the development of analytical techniques, based on physicochemical properties, to detect and measure the molecule produced in biochemical reactions. It is this ability to measure a substance like PAF specifically, apart from biological assays, that can be the foundation of a more complete understanding of the role that this substance plays as a lipid mediator of biologic events.


Molecular Species Chemical Synthesis Chemical Ionization Fast Atom Bombardment Ether Lipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Barber, M., Bordoli, R. S., Sedgwick, R. D., and Tyler, A. N., 1981, Fast atom bombardment of solids as an ion source in mass spectrometry, Nature 293:270–275.CrossRefGoogle Scholar
  2. Blank, M. L., Snyder, F., Byers, L. W., Brooks, B., and Muirhead, E. E., 1979, Antihypertensive activity of an alkyl ether analog of phosphatidylcholine, Biochem. Biophys. Res. Commun. 90:1194–1200.PubMedCrossRefGoogle Scholar
  3. Borrel, C., Broquet, C., Heymans, F., Michel E., Redeuilh C., Wichrowski, B., and Godfroid, J. J., 1982, Additional techniques for the total synthesis of PAF acether, Agents Actions 12:709–710.PubMedCrossRefGoogle Scholar
  4. Chacko, G. K., and Hanahan, D. J., 1969, Chemical synthesis of phosphonic acid monoether analog of phosphatidylethanolamine and phosphatidylcholine, Biochim. Biophys. Acta 176:190–199.PubMedGoogle Scholar
  5. Clay, K. L., Stene, D. O., and Murphy, R. C., 1984a, Quantitative analysis of platelet activating factor (AGEPC) by fast atom bombardment mass spectrometry, Biomed. Mass Spectrom. 11:47–49.CrossRefGoogle Scholar
  6. Clay, K. L., Murphy, R. C., Andres, J. L., Lynch, J., and Henson, P. M., 1984b, Structure elucidation of platelet activating factor derived from human neutrophils, Biochem. Biophys. Res. Commun. 121:815–825.PubMedCrossRefGoogle Scholar
  7. Demopoulos, C. A., Pinckard, N., and Hanahan, D. J., 1979, Platelet-activating factor. Evidence for l-0-alkyl-2-acetyl-srt-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators), J. Biol. Chem. 254:9355–9358.PubMedGoogle Scholar
  8. Egge, H., 1983, Mass spectrometry of ether lipids, in: Ether Lipids: Biochemical and Biomedical Aspects (H. K. Marshall and F. Paltauf, eds.), Academic Press, New York, pp. 17–47.Google Scholar
  9. Eibl, H., 1981, An improved method for the preparation of 1,2-isopropylidene-srt-glycerol, Chem. Phys. Lipids 28:1–9.CrossRefGoogle Scholar
  10. Godfroid, J-J., Heymans, F., Michel, E., Redeuilh, C., Steiner, E., and Benveniste, J., 1980, Platelet activating factor (PAF-acether): Total synthesis of l-0-octadecyl-2–0acetyl-5«-glycero-3-phosphorylcholine, FEBS Lett. 116:161–164.PubMedCrossRefGoogle Scholar
  11. Hanahan, D. J., Demopoulos, C. A., Liehr, J., and Pinckard, R. N., 1980, Identification of platelet activating factor isolated from rabbit basophils as acetyl glyceryl ether phosphorylcholine, J. Biol.Chem. 255:5514–5516.PubMedGoogle Scholar
  12. Haroldsen, P. E., Clay, K. L., and Murphy, R. C, 1987, Quantitation of lyso-platelet activating factor molecular species from human neutrophils by mass spectrometry, J. Lipid Res. 28:42–49.PubMedGoogle Scholar
  13. Heymans, F., Michel, E., Borrel, M-C., Wichrowski, B., Godfroid, JJ., Convert, D., Coeffier, E., Tence, M., and Benveniste, J., 1981, New total synthesis and high resolution 1H NMR spectrum of platelet-activating factor, its enantiomer and racemic mixtures, Biochim. Biophys. Acta 666:230– 237.PubMedGoogle Scholar
  14. Heymans, F., Borrel, M-C., Broquet, C., Lefort, J., and Godfroid, J-J., 1985, Structure-activity relationship in PAF-acether. 2. rac-l-0-octadecyl-2–0acetyl-3–0-[gamma-(dimethylamino)propyljglycol, J. Med. Chem. 28:1094–1096.PubMedCrossRefGoogle Scholar
  15. Hirth, G., Saroka, H., Bannwarth, W., and Barner, R., 1983, Synthese von glycerylatherphosphatiden, Helv. Chim. Acta 66:1210–1240.CrossRefGoogle Scholar
  16. Kanda, P. and Wells, M. A., 1980, A simplified procedure for the preparation of 2,3-O-isopropylidene-sn-glycerol from L-arabinose, J. Lipid Res. 21:257–258.PubMedGoogle Scholar
  17. Kertscher, H. P., 1983, Synthese von rac. l-0-hexadecyl-2–0acetylglycero-3-phosphocholin (PAF-acether), Pharmazie 38:421–422.Google Scholar
  18. Kohan, G., and Just, G., 1974, Simplified synthesis of 1,2,5,6-di-O-isopropylidene-D-mannitol, Synthesis 3:192.CrossRefGoogle Scholar
  19. Kumar, R., Weintraub, S. T., McManus, L. M., Pinckard, R. N., and Hanahan, D. J., 1984, A facile route to semi-synthesis of acetyl glycerylether phosphoethanolamine and its choline analogue, J. Lipid Res. 25:198–208.PubMedGoogle Scholar
  20. Marx, M. H., and Wiley, R. A., 1985, Synthesis of platelet activating factor (PAF) via a cyclic tin intermediate, Tetrahedron Lett. 26:1379–1380.CrossRefGoogle Scholar
  21. Mallet, A. I., and Cunningham, F. M., 1985, Structural identification of platelet activating factor in psoriatic scale. Biochem. Biophys. Res. Commun. 126:192–198.PubMedCrossRefGoogle Scholar
  22. Muramatsu, R., Totani, N., and Mangold, H. K., 1981, A facile method for the preparation of 1–0alkyl-2–0acetoyl-sn-glycero-3-phosphocholines (platelet activating factor), Chem. Phys. Lipids 29:121–127.CrossRefGoogle Scholar
  23. Murphy, R. C., and Harper, T. W., 1985, Mass spectrometry and eicosanoid analysis, in: Biochemistry of Arachidonic Acid Metabolism (W. E. M. Lands, ed.), Martinus Nijhoff Publishing, Boston, pp. 417–435.CrossRefGoogle Scholar
  24. Oda, M., Satouchi, K., Yasunaga, K., and Saito, K., 1985, Molecular species of platelet-activating factor generated by human neutrophils challenged with ionophore A23187, J. Immunol. 134:1090– 1093.PubMedGoogle Scholar
  25. Patton, G. M., Fasulo, J. M., and Robins, S. J., 1982, Separation of phospholipids and individual molecular species of phospholipids by high-performance liquid chromatography, J. Lipid Res. 23:190–196.PubMedGoogle Scholar
  26. Paltauf, F., 1983, Chemical synthesis of ether lipids, in: Ether Lipids: Biochemical Aspects (H. K. Mangold and F. Paltauf, eds.), Academic Press, New York, pp. 49–84.Google Scholar
  27. Pugh, E. L., Kates, M., and Hanahan, D. J., 1977, Characterization of the alkyl ether species of phosphatidylcholine in bovine heart, J. Lipid Res. 18:710–716.PubMedGoogle Scholar
  28. Ramesha, C. S., and Pickett, W. C., 1986, Measurement of subpicogram quantities of platelet activating factor (AGEPC) by gas chromatography-negative ion chemical ionization mass spectrometry. Biomed. Mass Spectrom. ,13:107– 111.CrossRefGoogle Scholar
  29. Reddy, P. V., Natarajan, V., and Sastry, P. S., 1976, Hydrolysis of sphingolyelin to ceramide with hydrofluoric acid, Chem. Phys. Lipids 17:373–377.PubMedCrossRefGoogle Scholar
  30. Satouchi, K., and Saito, K., 1977, Studies on trimethylsilyl derivatives of l-alk-l-enyl-2-acyl glycerols by gas liquid chromatography mass spectrometry, Biomed. Mass Spectrom. 4:107–110.PubMedCrossRefGoogle Scholar
  31. Satouchi, K., Oda, M., Yasunaga, K., and Saito, K., 1983, Application of selected ion monitoring to determination of platelet-activating factor, J. Biochem. 94:2067–2070.PubMedGoogle Scholar
  32. Satouchi, K., Oda, M., Yasunaga, K., and Saito, K., 1985, Evidence for production of l-acyl-2acetyl-sn-glyceryl-3-phosphorylcholine concomitantly with platelet-activating factor, Biochem. Bi ophys. Res. Commun. 128:1409–1417.CrossRefGoogle Scholar
  33. Snyder, F. (ed.), 1972, Ether Lipids: Chemistry and Biology ,Academic Press, New York.Google Scholar
  34. Strife, R. J., and Murphy, R. C., 1984, Preparation of pentafluorobenzyl esters of arachidonic acid lipoxygenase metabolites. Analysis by gas chromatography and negative ion chemical ionization mass spectrometry, .J. Chromatogr. 305:3–12.CrossRefGoogle Scholar
  35. Surles, J. R., Wykle, R. L., O’Flaherty, J. T., Salzer, W. L., Thomas, M. J., Snyder, F., and Piantodosi, C., 1985, Facile synthesis of platelet-activating factor and racemic analogues containing unsaturation in the sn-l-alkyl chain, J. Med. Chem. 28:73–78.PubMedCrossRefGoogle Scholar
  36. Tence, M., Polonsky, J, Le Couedic, J. P., and Benveniste, J., 1980, Release, purification and characterization of platelet-activating factor (PAF), Biochim. 62:251–259.CrossRefGoogle Scholar
  37. Varenne, P., Das, B. C., Polonsky, J., and Tence, M., 1985, Chemical ionization and fast atom bombardment mass spectrometry of platelet activating factor (PAF-acether) and related phospholipids, Biomed. Mass Spectrom. 12:6–10.CrossRefGoogle Scholar
  38. Voelkel, N. F., Simpson, J., Worthen, S., Reeves, J T., Henson, P. M., and Murphy, R. C., 1983, Platelet-activating factor causes pulmonary vasoconstriction and edema via platelet-independent leukotriene formation, in: Advances in Prostaglandin, Thromboxane and Leukotriene Research ,Volume 12 (B. Samuelsson, R. Paoletti, and P. Ranwell, eds.), Raven Press, New York, pp. 179– 183.Google Scholar
  39. Weintraub, S. Y., Ludwig, J. C., Mott, G. E., McManus, L. M., Lear, C., and Pinckard, R. N., 1985, Fast atom bombardment-mass spectrometric identification of molecular species of platelet-activating factor produced by stimulated human polymorphonuclear leukocytes, Biochem. Biophys. Res. Commun. 129:868–876.PubMedCrossRefGoogle Scholar
  40. Wells, M. A., and Hanahan, D. J., 1969, Studies on phospholipase A. I. Isolation and characterization of two enzymes from Crotalus adamanteus venom, Biochem. 8:414–424.CrossRefGoogle Scholar
  41. Wykle, R. L., Miller, C. H., Lewis, J. C., Schmitt, J. D., Smith, J. A., Surles, J. R., Piantodosi, C., and O’Flaherty, J. T., 1981, Stereospecific activity of l-O-alkyl-2-O-acetyl-sn-glycero-3-phos-phocholine and comparison of analog in the degranulation of platelets and neutrophils, Biochem. Biophys. Res. Commun. 100:1651–1658.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Robert C. Murphy
    • 1
  • Keith L. Clay
    • 1
  1. 1.Department of PharmacologyUniversity of Colorado Health Sciences CenterDenverUSA

Personalised recommendations