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CURRICULUM VITAE
KARL YODER HOSTETLER

EDUCATION
B.A. (Chemistry) cum laude, DePauw University, Greencastle, IN, 1961.
M.D., Western Reserve University, School of Medicine, Cleveland, OH, 1965.
APPOINTMENTS

Professor of Medicine, School of Medicine, University of California, San Diego, 1984-
Director, Endocrinology Clinic, San Diego VA Medical Center, 1995-
Staff Physician, San Diego VA Medical Center, 1973-2005; fee basis 2005-
Associate Member, Rebecca and John Moores Cancer Center, UCSD, 2003-
Founder and Director, Chimerix Inc., Durham, NC, 2002-2005; Consultant 2006-
Co-founder and Director, Triangle Pharmaceuticals, Inc., Durham, NC, 1995-98; Scientific Advisor 1995-1999
Founder, Director and Vice President, Research & Development, Vical Incorporated, San Diego, CA, 1987-1992;
Scientific Advisor 1992-1997.
Associate Professor of Medicine, School of Medicine, University of California, San Diego, 1979-1984
Assistant Professor of Medicine, School of Medicine, University of California, San Diego, 1973-1979
Clinical Investigator, Veterans Administration, 1983-1986
Acting Chief, Metabolism Section and Special Diagnostic and Treatment Unit, San Diego VA Medical Center, 1981-1983
San Diego VA Medical Center: Director, Metabolism Clinic, 1973-1983
U.S. Public Health Service Postdoctoral Trainee in Medicine (Lipid Biochemistry) with Dr. L.L.M. van Deenen, Utrecht,
Holland, July 1970- December 1972.
Special Fellow in Endocrinology and Metabolism, Cleveland Clinic Foundation, July 1969- June 1970
Assistant Resident, Department of Medicine University Hospitals of Cleveland, July 1969
Assistant Physician, Department of Medicine, University Hospitals of Cleveland, July 1966- June 1969
U.S. Public Health Service Postdoctoral Trainee in Medicine, Case Western Reserve University, July 1966- June 1969
Intern, Department of Medicine, University Hospitals of Cleveland, July 1965- June 1966
Investigator, Marine Biological Laboratories, Woods Hole, Massachusetts, 1962-1964; 1966-1968
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AWARDS

Fellow of the Japan Society for the Promotion of Science, 1986.
Distinguished Service Award, San Diego Federal Executive Association, 1984
Fellow of the John Simon Guggenheim Foundation, 1980-1981
Fogarty International Fellowship, 1980 (declined)
Service Award, American Diabetes Association, Southern California Affiliate, 1976
Invited Exchange Scientist, USSR Academy of Sciences, Shemyakin Institute of Bio-Organic Chemistry, Moscow, US -
USSR Health Sciences Exchange Program, 1974.
Faculty Award for Excellence in Research, Western Reserve University, School of Medicine, 1965.
Albert Steuer Memorial Award, Western Reserve University, School of Medicine, 1965
Samuel T. Haas Scholarship, Western Reserve University, School of Medicine, 1964-1965
C. Glen Barber Scholarship, Western Reserve University, School of Medicine, 1961-1965
MEMBERSHIPS

Associate Editor, The Journal of Clinical Investigation, 1993-1997
International Society For Antiviral Research, 1992-
American Society of Microbiology, 1992-
Endocrine Society, 1989-
American Society for Bone and Mineral Research 1988-
Editorial Board, Journal of Lipid Research, 1985-1996
Western Association of Physicians, 1984-
Western Society Clinical Investigation, 1983-
American Society for Clinical Investigation, 1981-
American Association for the Advancement of Science, 1976-
American Society Biochemistry and Molecular Biology, 1976-
American Federation for Clinical Research, 1973-

MEDICAL LICENSURE

1965 - Licensed to practice in Ohio
1973 - Licensed to practice in California
1974 - Diplomate, American Board of Internal Medicine
1975 - Diplomate, American Board of Endocrinology & Metabolism

COMMUNITY SERVICE

Board of Directors, San Diego Chamber Orchestra, 1985-1988; 1997-98
Del Mar Hills School Site Council, 1984-1986
President, Riveria Del Mar Homeowners Association, 1984-1986
President, San Diego Chapter, American Diabetes Association, 1982-1983
Board of Directors of the American Diabetes Association (San Diego Chapter), 1976-1984
Board of Directors, American Diabetes Association (Southern California Affiliate) 1975-1984
Consulting Endocrinologist (voluntary); Saint Vincent DePaul Village Free Medical Clinic, San Diego, CA
1997-2007
PUBLICATIONS

1. Lazarow,A., Dixit, P.K., Lindall, A., Moran, J., Hostetler, K.Y. and Cooperstein, S.J.: Enzyme specialization of islet
tissue in the structure and metabolism of the pancreatic islets, S.E., Brolin, B. Hellman, and H. Knutson, Eds. Oxford:
Pergamon, 1964.
2. Hostetler, K.Y., Cooperstein, S.J., Landau, B.R. and Lazarow, A.: Pathways of glucose metabolism in the isolated islet
of the goosefish in vitro. Am. J. Physiol., 211:1057-1062, 1966.
3. Hostetler, K.Y. and Landau, B.R.: Estimation of the pentose cycle contribution of glucose metabolism in tissues in
vivo
. Biochemistry, 6:2961, 1967.
4. Hostetler, K.Y. and Haynes, R.C.: Effect of triamcinolone on acetate 14C incorporation into fatty acids in liver. Fed.
Proc., 27:2304, 1968.
5. Hostetler, K.Y., Williams, H.R., Shreeve, W.W. and Landau, B.R.: Conversion of specifically 14C-labeled lactate and
pyruvate to glucose in man. J. Biol. Chem., 244:2075-2077, 1969.
6. Hostetler, K.Y., Landau, B.R., White, R.J., Albin, M.S. and Yashon, D.: Contribution of the pentose cycle to the
metabolism of glucose in the isolated, perfused brain of the monkey. J. Neurochem., 17:33-39, 1970.
7. Hostetler, K.Y. and Williams, H.R.: Effects of hyperglycemia, tolbutamide and glucagon on the pathways of glucose
oxidation in the goosefish islet, in vitro. Diabetes, 19:554-558, 1970.
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8. Hostetler, K.Y. and Haynes, R.C., Jr.: Effect of L-epinephrine and triamcino lone on the incorporation of acetate-2-14C and 32Pi into phospholipids and neutral lipids in liver slices from adrenalectomized rats, in vitro. Endocrinology, 87:1351-1354, 1970. 9. Ter Schegget, J., van den Bosch, H., van Baak, M.A., Hostetler, K.Y. and Borst, P.: The synthesis and utilization of dCDP-diglyceride by a mitochondrial fraction from rat liver. Biochim. Biophys. Acta, 239:234-242, 1971. 10. Hostetler, K.Y., van den Bosch, H. and van Deenen, L.L.M.: Biosynthesis of cardiolipin in liver mitochondria. Biochim. Biophys. Acta, 239:113-119, 1971. 11. Victoria, E.J., van Golde, L.M.G., Hostetler, K.Y., Scherphof, G.L. and van Deenen, L.L.M.: Some studies on the metabolism of phospholipids in plasma membranes from rat liver. Biochim. Biophys. Acta, 239:443-457, 1971. 12. Landau, B.R., Marshal , J.S., Craig, J.W., Hostetler, K.Y. and Genuth, S.M.: Quantitation of the pathways of fructose metabolism in normal and fructose-intolerant subjects. J. Lab. Clin. Med., 78:608-618, 1971. 13. Hostetler, K.Y. and van den Bosch, H.: Subcellular and submitochondrial localization of cardiolipin biosynthesis of cardiolipin and related phospholipids in rat liver. Biochim. Biophys. Acta, 260:380-386, 1972. 14. Hostetler, K.Y., van den Bosch, H. and van Deenen, L.L.M.: The mechanism of cardiolipin biosynthesis in liver mitochondria. Biochim. Biophys. Acta, 260:507-513, 1972. 15. Hostetler, K.Y., van den Bosch, H. and van Deenen, L.L.M.: Mechanism of cardiolipin biosynthesis in mitochondria. Abstr. Comm. Meet. Fed. Eur. Biochem. Soc., 8:1114, 1972. 16. Poorthuis, B.J.H.M. and Hostetler, K.Y.: Biosynthesis of bis(monoacylglyceryl)-phosphate and acylphosphatidylglycerol in rat liver mitochondrial prepara tions. J. Biol. Chem., 250:3297-3302, 1975. 17. Hostetler, K.Y., Galesloot, J.M., Boer, P. and van den Bosch, H.: Further studies on the formation of cardiolipin and phosphatidylglycerol in rat liver mitochondria: Effect of divalent cations and the fatty acid composition of CDP-diglyceride. Biochim. Biophys. Acta, 380:382-389, 1975. 18. Poorthuis, B.J.H.M. and Hostetler, K.Y.: Localization and properties of bis(monoacylglyceryl)phosphate synthesis in liver subcellular fractions. Clin. Res., 24:119A, 1976. 19. Poorthuis, B.J.H.M. and Hostetler, K.Y.: Studies on the nucleotide diphosphate diacylglycerol specificity of acidic phospholipid biosynthesis in rat liver subcellular fractions. Biochim. Biophys. Acta, 431:408-415, 1976. 20. Poorthuis, B.J.H.M., Yazaki, P.J. and Hostetler, K.Y.: An improved two dimensional thin-layer chromatography system for the separation of phosphatidylglycerol and its derivatives. J. Lipid Res., 17:433-437, 1976. 21. Poorthuis, B.J.H.M. and Hostetler, K.Y.: Studies on the subcellular localization and properties of bis(monoacylglyceryl)phosphate biosynthesis in rat liver. J. Biol. Chem 251:4596-4602, 1976. 22. Hostetler, K.Y. and Zenner, B.D.: Abnormal membrane phospholipid content in subcellular fractions from the Morris 7777 hepatoma. Biochim. Biophys. Acta, 441:231-238, 1976. 23. Hostetler, K.Y., Zenner, B.D. and Morris, H.P.: Increased mitochondrial CTP: Phosphatidic acid cytidyltransferase in 7777 hepatoma. Biochem. Biophys. Res. Comm 72:418-425, 1976. 24. Dyatlovitskaya, E.V., Hostetler, K.Y., Einisman, L.I. and Gorkova, N.P.: Biosynthesis of cardiolipin in the rat hepatoma 27 and the Jensen sarcoma. Biokhimia, 41:1421-1425, 1976, (in Russian). 4 25. Hostetler, K.Y., Hoppel, C.L., Romine, J.S., Sipe, J.C., Gross, S. and Higgin bottom, P.: Recurrent myoglobinuria due to a specific deficiency of carnitine palmitoyltransferase A in skeletal muscle mitochondria. Clin. Res., 25:l25A, 1977. 26. Poorthuis, B.J.H.M. and Hostetler, K.Y.: Lysosomal bis(monoacylglyceryl)phos phate synthesis requires a phospholipid acyl donor. Fed. Proc., 36:3051, 1977. 27. Hostetler, K.Y., Hoppel, C.L., Romine, J.S., Sipe, J.C., Gross, S. and Higginbottom, P.: Lipid myopathy with recurrent myoglobinuria due to carnitine palmitoyltransferase A deficiency in skeletal muscle mitochondria. Clin. Res., 25:496A, 1977. 28. Poorthuis, B.J.H.M. and Hostetler, K.Y.: Conversion of diphosphatidylglycerol to bis(monoacylglyceryl)phosphate by lysosomes. J. Lipid Res., 19:309-315, 1978. 29. Hostetler, K.Y., Hoppel, C.L., Romine, J.S., Sipe, J.C., Gross, S. and Higginbottom, P.: Partial deficiency of muscle carnitine palmitoyltransferase with normal ketone production. New Eng. J. Med., 298:553-557, 1978. 30. Hostetler, K.Y. and Yazaki, P.J.: Sphingomyelin hydrolysis by rat liver plasma membranes, Fed. Proc., 37:3101, 1978. 31. Hostetler, K.Y., Zenner, B.D. and Morris, H.P.: Altered subcellular and submitochondrial localization of CTP: Phosphatidate cytidyltransferase in the Morris 7777 hepatoma. J. Lipid Res., 19:553-560, 1978. 32. Matsuzawa, Y., Poorthuis, B.J.H.M. and Hostetler, K.Y.: Mechanism of phosphatidylinositol stimulation of lysosomal bis(monoacylglycero)-phosphate synthesis. J. Biol. Chem., 253:6650-6653, 1978. 33. Hostetler, K.Y. and Poorthuis, B.J.H.M.: Acidic phospholipids and lysosomal bis(monoacylglyceryl)phosphate synthesis: The role of phosphatidylinositol and lysophosphatidylglycerol, in "Cyclitols and Phosphoinositides," Frank Eisenberg, Jr. and William W. Wells, Eds, Academic Press, New York: 1978, pp. 585-597. 34. Hostetler, K.Y. and Yazaki, P.J.: The subcellular localization of neutral sphingomyelinase in rat liver. J. Lipid Res., 20:456-463, 1979. 35. Matsuzawa, Y. and Hostetler, K.Y.: Isolation and characterization of lamellar bodies from the liver of rats treated with chloroquine or 4,4`-diethylaminoethoxy-hexestrol. Fed. Proc., 38:1863, 1979. 36. Hostetler, K.Y., Zenner, B.D. and Morris, H.P.: Phosphatidylserine biosynthesis in mitochondria from the Morris 7777 hepatoma. J. Lipid Res., 20:607-613, 1979. 37. Matsuzawa, Y. and Hostetler, K.Y.: Degradation of bis(monoacylglycero)phosphate by an acid phosphodiesterase in rat liver lysosomes. J. Biol. Chem., 254:5997-6001, 1979. 38. Hostetler, K.Y., Zenner, B.D. and Morris, H.P.: Phospholipid content of mitochondria and microsomal membranes from Morris hepatomas of varying growth rates. Cancer Res., 39:2978-2983, 1979. 39. Matsuzawa, Y. and Hostetler, K.Y.: Mechanism of lysosomal hydrolysis of bis(monoacylglycero)phosphate. Proc. XI Int. Congress. Biochem., 11:377, 1979. 40. Matsuzawa, Y. and Hostetler, K.Y.: Studies on drug-induced lipidosis: Subcellular localization of phospholipid and cholesterol in the liver of rats treated with chloroquine or 4,4'-bis(diethylaminoethoxy)- ,ß-diethyldiphenylethane. J. Lipid Res., 21:202-214, 1980. 41. Matsuzawa, Y. and Hostetler, K.Y.: Properties of phospholipase C isolated from rat liver lysosomes. J. Biol. Chem. 255:646-652, 1980. 42. Matsuzawa, Y. and Hostetler, K.Y.: Inhibition of lysosomal phospholipase A and phospholipase C by chloroquine and 4,4'-bis(diethylaminoethoxy)- ,ß-diethyldiphenylethane, J. Biol. Chem., 255:5190-5194, 1980. 43. Hostetler, K.Y. and Yazaki, P.J.: Deficiency of carnitine palmitoyltransferase in transformed lymphoblasts from a patient having a deficiency of carnitine palmitoyltransferase in skeletal muscle. Biochem. Biophys. Res. Comm., 94:270-277, 1980. 44. Poorthuis, B.J.H.M., van der Krift, T.P., Teerlink, T., Hostetler, K.Y. and Wirtz, K.W.A.: Phospholipid transfer activities in Morris hepatomas and the specific contribution of the phosphatidylcholine exchange protein. Biochim. Biophys. Acta, 600:376-386, 1980. 45. Hostetler, K.Y. and Hall, L.B.: Phospholipase C activity of rat tissues. Biochem. Biophys. Res. Comm., 96:388-393, 1980. 46. Matsuzawa, Y. and Hostetler, K.Y.: Effects of chloroquine and 4,4'-bis(diethylaminoethoxy)- ,ß-diethyldiphenylethane on the incorporation of [3H]glycerol into the phospholipids of rat liver lysosomes an other subcellular fractions, in vivo. Biochim. Biophys. Acta, 620:592-602, 1980. 47. Hostetler, K.Y. and Matsuzawa, Y.: Chloroquine and 4,4`-diethylaminoethoxy-hexestrol inhibit lysosomal phospholipase A and C. Fed. Proc., 39:1347, 1980. 48. Hoppel, C., Genuth, S., Brass, E., Fuller, R., and Hostetler, K.Y. Carnitine and Carnitine palmitoyltransferase in metabolic studies, in Carnitine Biosynthesis, Metabolism and Functions, R.A. Frenkel and J.D. McGarry, Eds, Academic Press, New York: 1980, p. 287-305. 49. Hostetler, K.Y. and Hall, L.B.: Phospholipase C in rat tissues, in vitro. Fed. Proc., 39:2033, 1980. 50. Hostetler, K.Y. and Yazaki, P.J.: Phospholipase A activity in human skin fibroblasts, in vitro. Abstr. Comm. Meet. Fed. Eur. Biochem. Soc., 13:215, 1980. 51. Hostetler, K.Y. and Matsuzawa, K.: Studies on the mechanism of drug-induced lipidosis. Cationic amphiphilic drug inhibition of lysosomal phospholipases A and C. Biochem. Pharm., 30:1121-1126, 1981. 52. Richman, D.D., Yazaki, P.J. and Hostetler, K.Y.: The intracellular distribution and antiviral activity of amantadine. Virology, 111:81-90, 1981. 53. Hostetler, K.Y. and Hall, L.B.: Aminoglycoside antibiotics inhibit lysosomal phospholipase A and C from rat liver in vitro. Biochim. Biophys. Acta, 710:506-509, 1982. 54. Hostetler, K.Y. and Hall, L.B.: Inhibition of kidney lysosomal phospholipases A and C by aminoglycoside antibiotics: Possible mechanism of aminoglycoside toxicity. Proc. Nat. Acad. Sci. USA. 79:1663-1667, 1982. 55. Hostetler, K.Y., Yazaki, P.J., and van den Bosch, H.: Purification of lysosomal phospholipase A: Evidence for multiple isoenzymes in rat liver. J. Biol. Chem., 257:13367-13373, 1982. 56. Hostetler, K.Y. and Richman, D.D.: Studies on the mechanism of phospholipid storage induced by amantadine and chloroquine in Madin Darby canine kidney cells. Biochemical Pharmacol, 31:3795-3799, 1982. 57. Hostetler, K.Y.: Polyglycerophospholipids: Diphosphatidylglycerol, phosphatidylglycerol and bis(monoacylglycero)phosphate, in "Phospholipids, Comprehensive Biochemistry," J.N. Hawthorne, Editor, Elsevier-North Holland, Amsterdam: 1982, p. 215-261. 58. Hostetler, K.Y., Intracellular phospholipid and cholesterol metabolism in Morris hepatomas, in "Membranes in Tumor Growth," T. Galeotti, A. Cittadini, G. Neri and S. Papa, Eds. Elsevier Biomedical, Amsterdam, 1982, p. 481-492. 59. Hostetler, K.Y. and Hall, L.B.: Inhibition of kidney lysosomal phospholipases by aminoglycosides: A possible mechanism in nephrotoxicity. Clin. Res., 30:78A, 1982. 60. Hostetler, K.Y. and Richman, D.D.: Mechanisms of drug-induced lipidosis in cultured kidney cells. Clin. Res., 30:487A, 1982. 61. Vanheusden, G.P.H., van der Krift,T.P., Hostetler, K.Y. and Wirtz, K.W.A.: Effect of nonspecific phospholipid transfer protein on cholesterol esterification in microsomes from Morris hepatomas. Cancer Res., 43:4207-4210, 1983. 62. Hostetler, K.Y. and Pappu, A.: Inhibition of neutral and acidic phospholipase degradation by cationic amphiphilic drugs. Fed. Proc. 42:4947, 1983. 63. Pappu, A., Yazaki, P.J. and Hostetler, K.Y.: Inhibition of purified lysosomal phospholipae A1 by beta adrenergic blockers. Clin. Res., 31:252A, 1983. 64. Hostetler, K.Y. and Wolgast, D.M.: Kidney lysosomal phospholipase A1 and aminoglycoside nephrotoxicity. Clin. Res., 31:515A, 1983. 65. Fukunga, M., Miller, M.M., Hostetler, K.Y. and Deftos, L.J.: Effect of lipo some entrapment on the hypocalcemic action of parenterally administered calcitonin. Proceeding of the 65th Annual meeting of the Endocrine Society, June 8-10, 1983, #1204. 66. Nalbone, G. and Hostetler, K.Y.: Phospholipase A activity in two populations of rat heart mitochondria. Fed. Proc. 42:869, 1983. 67. Reasor, M.J. and Hostetler, K.Y.: Chloroquine treatment does not cause phospholipid storage by depleting rat liver lysosomes of acid phospholipase A. Biochim. Biophys. Acta, 793:497-501, 1984. 68. Pappu, A. and Hostetler, K.Y.: Effect of cationic amphiphilic drugs on the hydrolysis of acidic and neutral phospholipids by liver lysosomal phospholipase A. Biochem. Pharmacol., 33:1639-1644, 1984. 69. Fukanaga, M., Miller, M.M., Hostetler, K.Y. and Deftos, L.J.: Liposome entrapment enhances the hypocalcemic action of parenterally administered calcitonin. Endocrinol., 115(2):757-761, 1984. 70. Hostetler, K.Y.: Molecular studies on the induction of cellular phospho lipidosis by cationic amphiphilic drugs. Fed. Proc., 43:2582-2585, 1984. 71. Reasor, M.J., and Hostetler, K.Y.: Chloroquine-induced phospholipidosis in rat liver: Effects on acid phospholipase A activity. Toxicologist 4:43, 1984. 72. Hostetler, K.Y., Pappu, A.S. and Witztum, L.J.: Reduced postheparin lipoprotein lipase in drug-induced hypertriglyceridemia in guinea pigs. Clin. Res. 32:85A, 1984. 73. Hostetler, K.Y., Reasor, M.J. and Frazee, B.W.: Mechanisms of amiodarone pulmonary toxicity. Clin. Res. 32:528A, 1984. 74. Hostetler, K.Y., Reasor, M.J. and Frazee, B.W.: Mechanisms of amiodarone toxicity: inhibition of phospholipase A. Circulation 70: Suppl II., 957, 1984. 75. Nalbone, G. and Hostetler, K.Y.: subcellular localization of the phospholipases A of rat heart: Evidence for a cytosolic phospholipase A1. J. Lipid Res., 26:104-114, 1985. 76. Hostetler, K.Y., Pappu, A.S. and Witztum, J.L.: Diethylaminoethoxyhexestrol causes severe hypertriglyceridemia in guinea pigs. Biochim. Biophys. Acta 833:165-169, 1985. 77. Pappu, A., Yazaki, P.J. and Hostetler, K.Y.: Inhibition of purified lysosomal phospholipase A1 by various beta andrenergic blockers. Biochem. Pharmacol., 34:521-524, 1985. 78. Hostetler, K.Y., Reasor,M.J. and Yazaki, P.J.: Chloroquine-induced phospholipid fatty liver: Measurement of drug and lipid concentrations in rat liver lysosomes. J. Biol. Chem. 260:215-219, 1985. 79. Kubo, M. and Hostetler, K.Y.: Mechanism of cationic amphiphilic drug inhibition of purified lysosomal phospholipase A1. Biochemistry, 24:6515-6520, 1985. 80. Hostetler, K.Y.: The role of phospholipases in human diseases, in "Phospholipids and Cellular Regulation" Vol. 1, J.F. Kuo, Ed., CRC Press, Atlanta, 1985, p. 181-206. 81. Kubo, M., Reasor, M.J. and Hostetler, K.Y.: Mechanisms of chloroquine toxicity: Inhibition of lysosomal phospholipase A. Clin. Res. 33:91A, 1985. 82. Reasor, M.J., Walker, E.J. and Hostetler, K.Y.: Amiodarone-induced phospholipidosis in rats. Toxicologist. 5:48, 1985. 83. Kubo, M. and Hostetler, K.Y.: Inhibition of lysosomal phospholipase A1: role of drug binding to substrate. Clin. Res. 33:528A, 1985. 84. Kubo, M. and Hostetler, K.Y.: Measurement of gentamicin and propranolol binding to small unilamellar phospholipid vesicles. Clin. Res. 33:586A, 1985. 85. Kubo, M. and Hostetler, K.Y.: Drug-induced lipidosis: Mechanism of inhibition of phospholipase A1 and the role of drug binding to substrate. Proc. 13th Int. Cong. Biochem. MO-631, 1985. 86. Hostetler, K.Y., Reasor, M.J., Walker, E.R., Yazaki, P.J. and Frazee, B.W. Role of phospholipase A inhibition in amiodarone pulmonary toxicity in rats. Biochim. Biophys. Acta, 875:400-405, 1986. 87. Kubo, M., Gardner, M.F. and Hostetler, K.Y. Binding of propranolol and gentamicin to small unilamellar phospholipid vesicles: contribution of ionic and hydrophobic forces. Biochem. Pharmacol. 35:3761-3765, 1986. 88. Hostetler, K.Y., Gardner, M.F. and Giordano, J. Purification of lysosomal phospholipase A and demonstration of proteins that inhibit phospholipase A in a lysosomal fraction from rat kidney cortex. Biochemistry 25:6456-6461, 1986. 89. Richman, D.D., Hostetler, K.Y., Yazaki, P.J. and Clark, S. Fate of influenza A virion proteins after entry into subcellular fractions of LLC cells and the effect of amantadine. Virology, 151:200-210, 1986. 90. Nalbone, G., Hostetler, K.Y., Leonardi, J., M. Trotz., and H. Lafont. Partial characterization of rat heart cytosolic phospholipase A1: and demonstration of essential sulfhydryl groups. Biochim. Biophys. Acta. 877:88-95, 1986. 91. Hostetler, K.Y.: Phospholipid fatty liver: an acquired disease of impaired phospholipid catabolism, in Lipids and Biomembranes: Past, Present and Future," J.A.F. op den Kamp, B. Roelofsen and K.W.A. Wirtz Editors, Elsevier Science Publishers, Amsterdam, pp. 307-324, 1986. 92. Nalbone, G., Hostetler, K.Y., Leonardi, J., and Lafont, H.: Partial characterization of the cytosolic phospholipase A1 of rat heart. in: Enzymes of Lipid Metabolism II, L. Freysz, H. Dreyfus, R. Massarelli and S. Gatt, Eds. Plenum Publishing Corporation, New York, 1986, p. 153-157. 93. Hostetler, K.Y. and Jellison, E.J.: Propranolol inhibits phospholipase A of dog heart sarcoplasmic reticulum. Clin. Res. 34:89A, 1986. 94. Hostetler, K.Y. and Kubo, M.: Propranolol is a noncompetitive inhibitor of lipoprotein lipase. Clin. Res. 34:683A, 1986. 95. Hostetler, K.Y. and Aldern, K.A.: Amiodarone increases the phospholipid content of cultured human lymphoblasts. Circulation 74:Suppl II, 61, 1986. 96. Kubo, M. and Hostetler, K.Y. Metabolic basis of diethylaminoethoxyhexestrol-induced phospholipid fatty liver. Am. J. Physiol. 252:E375-379, 1987. 97. Kubo, M. and Hostetler, K.Y. Diethylaminoethoxyhexestrol inhibition of purified rat liver lysosomal phospholipase A1: Role of drug binding to substrate. J. Pharmacol. Exp. Therapeutics, 240:88-92, 1987. 98. Kubo, M. and Hostetler, K.Y. Inhibition of purified bovine milk lipoprotein lipase by propranolol and other ß-adrenergic blockers in vitro. Biochim. Biophys. Acta. 918:168-174, 1987. 99. Trotz, M., Jellison, E.J. and Hostetler, K.Y. Propranolol inhibition of the neutral phospholipases A of rat heart mitochondria, sarcoplasmic reticulum and cytosol. Biochemical Pharmacology, 36:4251-4256, 1987. 100. Hostetler, K.Y., Giordano, J.R. and Jellison, E.J. In vitro inhibition of lysosomal phospholipase A1 of rat lung by amiodarone and desethylaminodarone. Biochim. Biophys. Acta. 959:316-321, 1988. 101. Richman, D.D., Mitsuya, H., Broder, S. and Hostetler, K.Y. Fusidic acid, HIV, and host cell toxicity. Lancet, i, 1051-1052, 1988. 102. Trotz, M., Hein, L., and Hostetler, K.Y. Solubilization and partial characterization of phospholipase A from rat heart sarcoplasmic reticulum. Biochim. Biophys. Acta, 962:248-257, 1988. 103. Hostetler, K.Y. and Jellison, E.J. Cardiac phospholipases A: subcellular localization, properties and effects of selected inhibitors. Proceedings of the 2nd International Symposium on Lipid Metabolism in the Normoxic and Ischemic Heart, Maastricht, September, 1988. 104. Hostetler, K.Y. and Jellison, E.J. Evidence that aminoglycoside inhibition of lysosomal phospholipase a occurs by substrate depletion. Proceedings of the 14th International Congress of Biochemistry, TU:222, 1988. 105. Hostetler, K.Y. and Jellison, E.J. Evidence that aminoglycoside inhibition of lysosomal phospholipase A occurs by substrate depletion. J. Cell. Biochem. Suppl 12E, S-319, 1988. 106. Kihara, S., Kubo, M., Ikeda, N., Yokoyama, S., Matsuzawa, Y., Tarui, S., Yamamoto, A. and Hostetler, K.Y. Inhibition of purified human postheparin lipoprotein lipase by beta adrenergic blockers in vitro. Biochemical Pharmacology, 38:407-411, 1989. 107. Hostetler, K.Y. and Jellison, E.J. Role of phospholipases in myocardial ischemia: effect of cardioprotective agents on the phospholipases A of heart cytosol and sarcoplasmic reticulum in vitro. Mol. Cell Biochem., 88:77-82, 1989. 108. Hostetler, K.Y. and Richman, D.D. Inhibition of HIV replication by novel phospholipid derivatives of AZT and other antiretroviral nucleosides in vitro. Proceedings of the 5th International Conference on AIDS, Th.C.O.18, p. 536, 1989. 109. Hostetler, K.Y., Felgner, P.L., Wright, K. and Gardner, M.F. Prolonged hypocalcemia in rats treated with a sustained release form of human calcitonin. J. Bone Mineral Res. 4:Suppl. 1, 908, 1989. 110. Hostetler, K.Y. Synthesis and antiretroviral activity of novel phospholipid analogs of azidothymidine. Proc. Royal Dutch Academy of Science Workshop on Intracellular and Intravascular Lipid Transport, VI, 3, October, 1989. 111. Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H. and Richman, D.D. Synthesis and antiretroviral activity of phospholipid analogs of azidothymidine and other antiviral nucleosides. J. Biol. Chem., 265:6112-6117, 1990. 112. Hostetler, K.Y. and Jellison, E.J. Inhibition of kidney lysosomal phospholipase A1 by aminoglycosides is a novel variant of substrate depletion inhibition. J. Pharmacol. Exp. Ther., 254:188-191, 1990. 113. Hostetler, K.Y., van den Bosch, H., van Wijk, B., Stuhmiller, L.M. and Richman, D.D. Enhanced inhibition of HIV replication by dideoxythymidine diphosphate diglyceride in HT4-6C cells in vitro. Clin. Res. 38: 115A, 1990. 114. Li, J.L., Felgner, P.L., Richman, D.D. and Hostetler, K.Y. Comparative therapeutic effects of AZT and liposomal AZT-monophosphate in murine retrovirus-induced immunodeficiency disease. J. Cell. Biochem., Suppl. 14D, p. 172, 1990. 115. Hostetler, K.Y., van den Bosch, H., van Wijk, B., Stuhmiller, L.M. and Richman, D.D. Phospholipid derivatives of dideoxythymidine (ddT) exhibit greatly increased potency against replication of HIV in CD4-HeLa cells. J. Cell Biochem., Suppl. 14D, p. 152, 1990. 116. van Wijk, G.M.T., Hostetler, K.Y. and van den Bosch, H. Nucleoside-diphosphate-diglycerides with anti-retroviral activity: Improved chemical synthesis and metabolic studies with rat liver subcellular fractions. Proc. Fed. Eur. Biochem. Soc., August 19-24, 1990. 117. Kumar, R., Richman, D.D. and Hostetler, K.Y. Effect of stereoisomers of lipid analogs of zidovudine (AZT) on HIV-infected HT4-6C cells. FASEB J., 4:(7), A2259, 1990. 118. Li, J-L., Felgner, P.L., Richman, D.D. and Hostetler, K.Y. Murine retrovirus-induced immunodeficiency disease: comparative effects of AZT and liposomal AZT-MP. Proc. 6th Internat. Conf. AIDS, vol. 1, p. 186, 1990. 119. Kumar, R., Richman, D.D. and Hostetler, K.Y. Antiretroviral effects of glycerophospholipid stereoisomers of AZT on HIV replication in HT4-6C cells. Proc. 6th Internat. Conf. AIDS, San Francisco, vol. 1, p. 186, 1990. 120. Stuhmiller, L.M., Hostetler, K.Y. and King, D.H. Synthesis and antiviral activity of phospholipid derivatives of 1-(2'-deoxy-2'- fluoro-ß-D-arabinofuranosyl)-5-iodouracil (FIAU) and 1-(2'-deoxy-2'-fluoro- ß-D-arabinofuranosyl)-5-iodocytosine (FIAC). Proc. 200th Annual Meeting Am. Chem. Soc. (Medicinal) 133, 1990. 121. Schlame, M., and Hostetler, K.Y. Mammalian Cardiolipin Biosynthesis. Methods in Enzymology, 1991, 209:330-337. 122. Hostetler, K.Y., Carson, D.A., and Richman, D.D. Phosphatidylazidothymidine. Mechanism of antiretroviral action in CEM cells. J. Biol. Chem., 266:11714-11717, 1991. 123. van Wijk, G.M.T., Hostetler, K.Y., and van den Bosch, H. Lipid conjugates of antiretroviral agents: release of antiretroviral nucleoside monophosphate by a nucleoside diphosphate diglyceride hydrolase activity from rat liver mitochondria. Biochim. Biophys. Acta, 1084:307-310, 1991. 124. Hostetler, K.Y. vande Berg, J., Aldern, K.A. and Brophy, G.T. Effect of amiodarone on the phospholipid and lamellar body content of lymphoblasts in vitro and peripheral blood lymphocytes, in vivo. Biochemical Pharmacology 41:1007-1013, 1991. 125. Hostetler, K.Y.: Effect of thyroxine on the activity of mitochondrial cardiolipin synthase in rat liver. Biochim. Biophys. Acta. 1086:139-140, 1991. 126. Schlame, M., and Hostetler, K.Y. Solubilization, purification, and characterization of cardiolipin synthase from rat liver mitochondria. Demonstration of its phospholipid requirement. J. Biol. Chem., 266:22398-22403, 1991. 127. Hostetler, K.Y., Aldern, K.A. and Gardner, M.F. Assay of phospholipase C and phospholipse D in the presence of other lipid hydrolases. Methods in Enzymology, 197:125-134, 1991. 128. Hostetler, K.Y. and Gardner, M.F. Purification of lysosomal phospholipase from rat kidney. Methods in Enzymology 197:325-330, 1991. 129. van Wijk, G.M.T., Hostetler, K.Y., Schlame, M., and van den Bosch, H. Cytidine diphosphate diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions. Biochim. Biophys. Acta, 1086:99-105, 1991. 130. van Wijk, G.M.T., Hostetler, K.Y. and van den Bosch, H. Lipid conjugates of antiretroviral agents: release of antiretroviral nucleoside monophosphates by a nucleoside diphosphate diglyceride hydrolase activity from rat liver mitochondria. Biochim Biophys Acta, 1084:307-310, 1991. 131. Hostetler, K.Y., Gardner, M.F., and Richman, D.D. PhosphatidylddC, A phospholipid prodrug of dideoxycytidine: antiviral properties and improved pharmacokinetics in mice. Proc. 7th Internat. Conf. AIDS, Florence, Italy, W.A.1001, 1991 132. van Wijk, G.M.T., Hostetler, K.Y., and van den Bosch, H. Phospholipid conjugates of dideoxynucleosides; the metabolism of dideoxycytidine- and 3'-deoxythymidine diphosphate diglyceride in rat liver. Proc. 7th Internat. Conf. AIDS, Florence, Italy, W.A.1092, 1991. 133. van Wijk, G.M.T., Hostetler, K.Y. and van den Bosch, H. Nucleoside diphosphate diglycerides: Improved synthesis and facilitated purification. J. Lipid Res., 33:1211-1217, 1992. 134. Kumar, R., Gardner, M.F., Kaliman, A., Richman, D.D. and Hostetler, K.Y. Equal inhibition of HIV replication by stereoisomers of phosphatidyl-AZT: Lack of stereospecificity of lysosomal phospholipase A1. J. Biol. Chem., 267:20288- 20292, 1992. 135. van Wijk, G.M.T., Gadella, T.W.J., Wirtz, K.W.A., Hostetler, K.Y. and van den Bosch, H. Sponteneous and protein-mediated intermembrane transfer of the antiretroviral liponucleotide 3'-deoxythymidine diphosphate diglyceride. Biochemistry, 31:5912-5917, 1992. 136. Hostetler, K.Y., Richman, D.D., Carson, D.A., Stuhmiller, L.M., van Wijk, G.M.T. and van den Bosch, H. Greatly enhanced inhibition of HIV-1 replication in CEM and HT4-6C cells by 3'-deoxythymidine diphosphate dimyristoylglycerol, a lipid prodrug of 3'-deoxythymidine. Antimicrob. Agents Chemotherapy, 36: 2025-2029, 1992. 137. Hostetler, K.Y. Phospholipid prodrugs of antiviral nucleosides and HIV protease inhibitors: synthesis and biological activity. J. Molecular Recognition, 5:24, 1992. 11 138. Wherrett, J.R., Hostetler, K.Y. and Huterer, S.J., Transacylation of bis(monoacyl-glycero)phosphate by lysosomes, Transactions Am.Soc. Neurochem., 23:311, 1992. 139. Schlame, M., Brody, S., and Hostetler, K.Y. Mitochondrial cardiolipin in diverse eukaryotes: Comparison of the biosynthesis and molecular acyl species. European J. Biochem., 212:727-735, 1993. 140. Huterer, S.J., Hostetler, K.Y., Gardner, M.F. and Wherrett, J.R. Lysosomal phosphatidylcholine: bis(monoacylglycero)phosphate acyltransferase: specificity for the sn-1 fatty acid of the donor and copurification with phospholipase A1, Biochim. Biophys. Acta, 1167:204-210, 1993. 141. Hostetler, K.Y., Parker, S., Sridhar, C.N., Martin, M.J., Li, J-L., Stuhmiller, L.M., van Wijk, G.M.T., van den Bosch, H. and Richman, D.D. Acyclovir diphosphate dimyristoylglycerol: A phospholipid prodrug with activity against acyclovir-resistant herpes simplex virus. Proc. Nat. Acad. Sci. USA, 90:11835-11839, 1993. 142. van Wijk, G.M.T., Hostetler, K.Y., Suurmeijer, C.N.S.P., and van den Bosch, H. Synthesis, characterization and some properties of cytidine diphosphate diglyceride analogs with antiretroviral activity. Biochim. Biophys. Acta, 1165:45-52, 1993. 143. Xie, H., Korba, B.E., Sridhar, C.N., Wheeler, C. and Hostetler, K.Y., Synthesis and antiviral activity of dipalmitoylphosphatidyldideoxyguanosine in hepatitis B virus infected cells, in vitro, FASEB J. 7:1448, 1993. 144. Hostetler, K.Y., Basava, C., Selk, L., Gardner, M., Parker, S. and Richman, D.D., HIV protease inhibitor lipid prodrug exhibits greatly prolonged plasma residence time in vivo, Proc. IX International Conference on AIDS, I:34, WS-A18-6, 1993. 145. Basava, C., Selk, L.M., Basava, R., Parker, S., Richman, D.D. and Hostetler, K.Y., Novel peptide prodrugs: lipid derivatization of protease inhibitor enhances in vivo plasma half life, Proc. 13th American Peptide Symposium, 1993. 146. van Wijk, G.M.T., Hostetler, K.Y., Kroneman, E. and van den Bosch, H. Synthesis and antiviral activity of 3'-azido-3'-deoxythymidine triphosphate distearoyl glycerol. A novel phospholipid conjugate of the anti-HIV agent AZT. Chemistry and Physics of Lipids, 70:213-222, 1994. 147. Hostetler, K.Y., Korba, B.E., Sridhar, C.N. and Gardner, M.F. Antiviral Activity of phosphatidyl-dideoxycytidine in hepatitis-B infected cells and enhanced hepatic uptake in mice, Antiviral Res., 24:59-67, 1994. 148. Hostetler, K.Y., Richman, D.D., Sridhar, C.N., Felgner, P.L., Felgner, J., Ricci, J., Gardner, M.F., Selseth, D. and Ellis, M.N., Phosphatidyl-dideoxycytidine and phosphatidyl-azidothymidine: assessment of uptake in mouse lymphoid tissues, antiviral activity in HIV-infected cells and in Rauscher leukemia virus infected mice, in vivo, Antimicrobial Agents Chemotherap., 38:2792-2797, 1994. 149. Hostetler, K.Y., Basava, C., Selk, L., Basava, R., Sridhar, C.N., Gardner, M.F., Parker, S., Forssen, E.A. and Richman, D.D., Synthesis, antiviral activity and pharmacokinetics in rats of a phospholipid prodrug HIV protease inhibitor, Biochem. Pharmacol., 48:1399-1404, 1994. 150. Xie, H., Liotta, D.C., Schinazi, R.F., Richman, D.D. and Hostetler, K.Y., Synthesis, purification and antiviral evaluation of a phospholipid conjugate of (-)-2'-deoxy-3'-thiacytidine (3TC) in vitro, Proc. 207th Mtg. Am. Chem. Soc. (Medicinal), 32, 1994. 151. Shakiba, S., Freeman, W.R., Flores-Aguilar, M., Munguia, D., Tatebayashi, M., Besen, G., Amani, R., Wiley, C.A., Vuong, C., Aldern, K.A., Gardner, M.F. and Hostetler, K.Y., Antiviral effect in human cytomegalovirus-infected cells, pharmacokinetics and intravitreal toxicology in rabbits of acyclovir diphosphate dimyristoylglycerol, Antimicrob. Agents Chemotherap., 39:1383-1385, 1995. 12 152. Xie, H., Voronkov, M., Liotta, D.C., Korba, B.A., Schinazi, R.F., Richman, D.D. and Hostetler, K.Y., Phosphatidyl-2',3'-dideoxy-3'-thiacytidine: synthesis and antiviral activity in hepatitis B and HIV-1 infected cells, Antiviral Res., 28:11-15, 1995. 153. Hostetler, K.Y., Aldern, K.A., Kini, G.D., Wheeler, C.J. and Sridhar, C.N., Phosphonoacid prodrugs with greatly increased antiviral activity in HCMV-infected cells, in vitro, Proc. 8th. Internat. Soc. Antiviral Res., Santa Fe, NM, 1995. 154. Hostetler, K.Y., Kini, G.D., Chou, T.-C. and Richman, D.D., 1-O-Octadecylglycerol-3-phosphonoformate exhibits enhanced activity and synergy with AZT against HIV, in vitro, Proc. 35th Intersci. Conf. Antimicrobial Agents & Chemotherapy, San Francisco, 1995. 155. Reasor, M.J., McCloud, C.M., Beard, T.L., Ebert D.C., Kacew, S., Gardner, M.F., Aldern, K.A. and Hostetler, K.Y., Comparative evaluation of amiodarone-induced phospholipidosis and drug accumulation in Fischer-344 and Sprague-Dawley rats, Toxicology., 106:139-147, 1996. 156. Kini, G.D., Beadle, J.R., Aldern, K.A. and Hostetler, K.Y., Synthesis and antiviral activity of stereoisomers of 1-O-octadecyl-sn-glycero-3-phosphonoformate, Proc. 210th American Chemical Society Meeting, 101, 1995. 157. Beadle, J.R., Kini, G.D., Aldern, K.A. and Hostetler, K.Y., Alkyl thioglycerol prodrugs of phosphonoformate, Proc. 210th American Chemical Society Meeting, 10, 1995. 158. Xie, H., Korba, B.A., Tennant, B.C. and Hostetler, K.Y., Antiviral activity of dideoxyguanosine and phosphatidyl-dideoxyguanosine in hepatitis B virus-infected cells and in woodchuck hepatitis virus infection in vivo, Hepatology, 23:958-963, 1996. 159. Hostetler, K.Y., Kini, G.D., Beadle, J.R., Aldern, K.A., Gardner, M.F., Border, R., Barshak, L., Kumar, R., Sridhar, C.N., Wheeler, C.J. and Richman, D.D., Lipid prodrugs of phosphonoacids: greatly enhanced antiviral activity of 1-O-octadecyl-sn-glycero-3- phosphonoformate in HIV-1, HSV-1 and HCMV-infected cells, in vitro, Antiviral Research, 31:59-67, 1996. 160. Taskintuna, I., Banker, A.S., Flores-Aguilar, M., Bergeron-Lynn, G., Aldern, K.A., Hostetler, K.Y. and Freeman, W.R., Evaluation of a novel lipid prodrug for intraocular drug delivery: effect of acyclovir diphosphate dimyristoylglycerol in a rabbit model with herpes simplex virus-1 retinitis, Retina , 17:57-64, 1997. 161. Hostetler, K.Y., Kini, G.D., Beadle, J.R., Aldern, K.A. and Richman, D.D., Antiviral activity of alkylglycerol foscarnet analogs in HIV-1 infected HT4-6C cells: structure-activity studies, 9th International Conf. on Antiviral Research, Fukushima, Japan, Antiviral Research, 30:A11, 1996. 162. Hostetler, K.Y., Beadle, J.R., Kini, G.D. Gardner, M.F., Wright, K.N., Wu, Tong-Hau, and Korba, B.A., Enhanced oral absorption and antiviral activity of 1-O-octadecyl-sn-glycero-3-phospho-acyclovir in hepatitis B virus infection, in vitro, Biochemical Pharmacology, 53:1815-1822, 1997. 163. Kini, G.D., Beadle, J.R., Xie, H., Aldern, K.A., Richman, D.D. and Hostetler, K.Y., Alkoxy Propane Prodrugs of Foscarnet: Effect of Alkyl Chain Length on In Vitro Antiviral Activity in Cells Infected with HIV-1, HSV-1 and HCMV, Antiviral Research, 36:43-53,1997. 164. Rosowsky, A., Fu, H.-N., Pai, N., Mellors, J.W., Richman, D.D. and Hostetler, K.Y., Synthesis and in vitro activity of long-chain 5'-(o-alkoxycarbonylphosphinytl)-3'-azido-3'-deoxythymidines against wild type and AZT- and foscarnet-resistant strains of human immunodeficiency type-1 virus (HIV-1), J. Medicinal Chem., 40:2482-2490, 1997. 165. Beadle, J.R., Kini, G.D., Aldern, K.A. and Hostetler, K.Y., Synthesis and antiviral activity of alkoxypropyl esters of ganciclovir monophosphate in HCMV and HSV-infected cells, Proc. 213th Am. Chemical Soc., 268, 1997. 166. Kini, G.D., Beadle, J.R., Aldern, K.A., Mellors, J.W., Richman, D.D. and Hostetler, K.Y., Lipid prodrug of a foscarnet-AZT conjugate: synthesis and antiviral activity against PFA- and AZT-resistant strains of HIV, Proc. 213th Am Chemical Soc., 283, 1997. 167. Rosowsky, A., Fu, H., Pai, N., Mellors, J.W., Richman, D.D. and Hostetler, K.Y. Synthesis and in vitro antiviral activity of long chain 5'-(o-alkoxycarbonylphosphinytl)-3'-azido-3'-deoxythymidines against wild type and AZT- and foscarnet-resistant strains of human immunodeficiency type-1 virus (HIV-1), Proc. 10th Internat. Conf. Antiviral Research, Atlanta, April 1997; Antiviral Res. 34(2): 10, 1997. 168. Schlame, M. and Hostetler, K.Y., Cardiolipin synthase from mammalian mitochondria, Biochim. Biophys. Acta, 1348:207-213, 1997 169. Beadle, J.R., Kini, G.D., Aldern, K.A., Gardner, M.F., Wright, K. and Hostetler, K.Y. Alkylthioglycerol prodrugs of foscarnet: oral bioavailability and structure-activity studies in human cytomegalovirus,herpes simplex virus type-1 and human immunodeficiency virus type-1 infected cells, Antiviral Chem. Chemotherap., 9:33-40, 1998. 170. Gardner, M.F. and Hostetler, K.Y. Improved method for the detection of ganciclovir in plasma using HPLC with electrochemical detection. Proc. 11th Internat. Conf. Antiviral Research, California, April 1998. 171. Aldern, K.A., Beadle, J.R., Kini, G.D., Stoddart, C.A. and Hostetler, K.Y. Antiviral activity of lipid prodrugs of foscarnet and ganciclovir against the AD169 and Toledo strains of human cytomegalovirus. Proc. 11th Internat. Conf. Antiviral Research, California, April 1998. 172. Wright, K.N., Gardner, M.F., Beadle, J.R., Kini, G.D. and Hostetler, K.Y. The effect of intraperitoneal injection of 1-O-octadecyl-sn-glycero-3-foscarnet on mortality and serum calcium levels in mice. Proc. 11th Internat. Conf. Antiviral Research, California, April 1998. 173. Beadle, J.R., Kini, G.D., Korba, B.E., Tennant, B.C. and Hostetler, K.Y. Phospholipid prodrugs of antiviral nucleosides: efficacy of orally administered 3-hexadecyloxypropane-1-phospho-acyclovir against hepatitis B infection in woodchucks. Proc. 11th Internat. Conf. Antiviral Research, California, April 1998. 174. Kini, G.D., Beadle, J.R., Aldern, K.A., Richman, D.D., Korba, B.E., Hostetler, K.Y. Anti-hepatitis B virus activity of 3-hexadecyloxypropane-1-phospho-penciclovir and 3-hexadecyloxypropane-1-phospho-dideoxyguanosine in 2.2.15 cells. Proc. 11th Internat. Conf. Antiviral Research, California, April 1998. 175. Cheng, L.Y., Hostetler, K.Y., Gardner, M.F., Avila, C.P., Bergeron-Lynn, G., Keefe, K.S., Munguia, D., Garcia, C., Freeman, W.R. Intravitreal toxicology of the 1-O-Octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA) and its carboxymethyl ester in liposome formulation. Investigative Ophthalmology and Visual Sciences, 39(4):S276, 1998. 176. Cheng, L.Y., Hostetler, K.Y., Gardner, M.F., Avila, C.P., Bergeron-Lynn, G., Keefe, K.S., Wiley, C.A., Freeman, W.R. Intravitreal toxicology in rabbits of two preparations of 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA) a sustained delivery anti-CMV drug. Investigative Ophthalmology and Visual Sciences. 40:1487-1495, 1999. 177. Cheng, L., Hostetler, K.Y., Gardner, M.F., Avila, C.P. Jr., Bergeron-Lynn, G., Severson, G.M. and Freeman, W.R. Intravitreal pharmacokinetics in rabbits of the foscarnet lipid prodrug: 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA). Current Eye Research 18(3):161-167, 1999. 178. Cheng, L., Hostetler, K.Y., Gardner, M.F., Avila Jr. C.P., Bergeron-Lynn, G., Keefe, K.S., Wiley, C.A. and Freeman, W.R. Intravitreal toxicology and therapeutic efficacy of the carboxymethyl ester of the 1-O-octadecyl-sn-glycerol-3-
phosphonoformate (ODG-PFA-OMe), a novel lipid anti-viral prodrug for intraocular drug delivery. Journal of Ocular
Therapeutics Pharmacokinetics, 15:363-377, 1999.
179. Cheng, L., Hostetler, K.Y., Chaidhawangul, S., Gardner, M.F., Ozerdem, U., Bergeron-Lynn, G., Mach-Hofacre, B.,
Mueller, A.J., Severson, G.M. and Freeman, W.R. Treatment of herpes retinitis in an animal model with sustained
delivery antiviral drug, liposomal 1-O-octadecyl-sn-glycero-3-phosphonoformate, Retina,19:325-331, 1999.
180. Hostetler, K.Y., Beadle, J.R., Hornbuckle, W.E., Bellezza, C.A., Tochkov, I.A., Korba, B.E. and Tennant, B.C., Oral
activity of 1-O-hexadecylpropanediol-3-P-acyclovir in woodchucks with chronic woodchuck hepatitis virus infection and
synergy with lamivudine, in vitro, Proc. 3rd Int. Conf. On Therapies for Viral Hepatitis, Dec. 1999.
181. Beadle, J.R., Kini, G.D., Aldern, K.A., Gardner, M.F., Wright, K.N., Ryback, R.J., Kern, E.R. and Hostetler, K.Y.
Synthesis and antiviral evaluation of 1-O-hexadecylpropanediol-3-P-acyclovir: Efficacy against HSV-1 infection in mice,
Nucleosides and Nucleotides, 19:471-480, 2000.
182. Kern, E.R., Palmer, J. Szczech, G., Painter, G. and Hostetler, K.Y. Efficacy of topical acyclovir or penciclovir in
orofacial HSV-1 infections of mice and genital HSV-2 infections of guinea pigs, Nucleosides and Nucleotides, 19:501-513,
2000.
183. Hostetler, K.Y., Beadle, J.R., Hostetler, S.E., Kini, G.D., Aldern, K.A., Richman, D.D., Hammond, J.L., Zonarich,
D.L., Bazmi, H.Z. and Mellors, J.W., Alkylglycerol foscarnet analogs are active in vitro at submicromolar concentrations
against a panel of drug resistant strains of HIV-1, Proc. 7th Conference on Retroviruses and Opportunistic Infections, Jan.
30- 2000.
184. Cheng, L., Hostetler, K.Y., Chaidhawangul, S., Gardner, M.F., Beadle, J.R., Keefe, K.S., Bergeron-Lynn, G.,
Severson, G.M., Soules, K.A., Mueller, A.J. and Freeman, W.R., Intravitreal toxicology and treatment efficacy of a long
acting antiviral lipid prodrug of ganciclovir in liposome formulation, Investigational Opthalmology & Visual Science,
41:1523-1532, 2000.
185. Hostetler, K.Y., Hammond, J.A., Kini, G.D., Hostetler, S.E., Beadle, J.R., Chou, T-C., Albanil, S., Richman, D.D. and
Mellors, J. Antiviral activity of sn-2 substituted 1-O-octadecyl-sn-glycero-3-foscarnet analogs and synergy with
zidovudine, in vitro. Antiviral Chemistry and Chemotherapy, 11:213-220, 2000.
186. Hostetler, K.Y., Beadle, J.R., Hornbuckle, W.E., Bellezza, C.A., Tochkov, I.A., Cote, P.J., Gerin, J.L., Korba, B.E.
and Tennant, B.C., Antiviral activity of oral 1-O-hexadecylpropanediol-3-P-ACV in woodchucks with chronic woodchuck
hepatitis virus infection, Antimicrobial Agents Chemotherapy, 44:1964-1969, 2000.
187. Hostetler, K.Y., Rybak, R.J., Beadle, J.R., Hartline, C.B., Gardner, M.F., Aldern, K.A., Wright, K. and Kern,
E.R., In Vitro and in Vivo Activity of 1-O-hexadecylpropanediol-3-phospho-ganciclovir and 1-O-hexadecylpropanediol-3-
phospho-penciclovir in Cytomegalovirus and Herpes Simplex Virus Infections, Antiviral Chemistry and Chemotherapy,
11:373-381, 2001.
188. Hammond, J.L., Koontz, D., Bazmi, H.Z., Beadle, J.R., Hostetler, S.E., Kini, G.D., Aldern, K.A., Richman, D.D.,
Hostetler, K.Y. and Mellors, J.W. Alkylglycerol prodrugs of phosphonoformate are potent in vitro inhibitors of nucleoside
resistant HIV type 1 and select for resistance mutations that reverse AZT resistance, Antimicrobial Agents
Chemotherapy, 45:1621-1628, 2001.
189. Kern, ER, Hartline, C, Harden E, Rodriguez, N, Beadle JR and Hostetler, KY, Enhanced inhibition of orthopoxvirus
replication in vitro by alkoxyalkyl esters of cidofovir and cyclic cidofovir, Proc. 14th Int. Conf. Antiviral Research, 2001.

190. Beadle, JR, Rodiguez, N, Aldern, KA and Hostetler, KY, Alkylglyceryl and Alkoxyalkyl Esters of Antiviral
Phosphonates, Proc. 14th Int. Conf. Antiviral Research, 2001.
15
191. Cheng, L, Hostetler, KY, Chaidhawangul, S, Gardern, MF, Beadle, JR, Bergeron-Lynn, G and Freeman WR, New Intraocular drug delivery system: Crystalline 1-O-Hexadecylpropanediol-3-P-Ganciclovir, Investigational Opthalmology & Visual Science, 43:515-521, 2002. 192. Kern, E.R., C. Hartline, C., Harden, E., Keith, K., Rodriguez, N, Beadle, J.R. and Hostetler, K.Y., Enhanced inhibition of orthopoxvirus replication in vitro by alkoxyalkyl esters of cidofovir and cyclic cidofovir, Antimicrobial Agents Chemotherapy, 46:991-995, 2002. 193. Ciesla, SL, Kim, H.S., Beadle, J.R. and Hostetler, K.Y., Synthesis and Anti-HIV activity of alkoxyalkyl esters of saquinavir phosphate, Antiviral Research, 53:A41(18), 2002. 194. Huggins, J.W., Baker, R.O., Beadle, J.R. and Hostetler, K.Y., Orally active ether lipid prodrugs of cidofovir for the treatment of smallpox, Antiviral Research, 53:A66(104), 2002. 195. Winegarden, K.L., Ciesla, S.L., Aldern, K.A., Beadle, J.R. and Hostetler, K.Y., Oral pharmacokinetics and preliminary toxicology of 1-O-hexadecyloxypropyl-cidofovir in mice, Antiviral Research, 53:A67(105), 2002. 196. Aldern, K.A., Ciesla, S.L., Winegarden, K.L. and Hostetler, K.Y., 1-O-Hexadecyloxypropyl-[14C]cidofovir: cellular uptake and metabolism in MRC-5 human lung fibroblasts, in vitro, Antiviral Research, 53:A62 (92), 2002. 197. Beadle, J.R., Rodriquez, N., Aldern, K.A., Hartline, C., Harden, E., Kern E.R. and Hostetler, K.Y. Alkoxyalkyl esters of cidofovir and cyclic cidofovir exhibit multiple log enhancement of antiviral activity against cytomegalovirus and herpesvirus replication, in vitro, Antimicrobial Agents Chemotherapy, 46:2381-2386, 2002. 198. Beadle, J.R., Cheng, L., Hostetler, K.Y. and Freeman, W.R., Phospholipid prodrugs of nucleosides for intravitreal injection: synthesis of hexadecyloxypropyl-phospho-Ara G for treatment of proliferative vitreoretinopathy, National meeting of the Association for Research Vision and Opthalmology (ARVO), Miami, 2002. 199. Wan, W.B., Beadle, J.R., Aldern, K.A. and Hostetler, K.Y., Alkoxyalkyl Esters of Cidofovir and cyclic cidofovir: effects of alkyl chain length, unsaturation and substitution on the in vitro antiviral activity in cells infected with HSV-1 and CMV, Presentation at the American Chemical Society, Medicinal Chemistry Meeting, Boston, MA, August 2002. 200. Wan, W.B., Beadle, J.R., Aldern, K.A., Keith, K., Kern, E.R. and Hostetler, K.Y., Alkoxyalkylesters of cidofovir with improved oral bioavailability and antiviral potency against cowpox and vaccinia viruses: In search of the optimal ester. Presentation at Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, September, 2002. 201. Aldern, K.A., Ciesla, S.L., Winegarden, K.L. and Hostetler, K.Y., The increased antiviral activity of 1-O-hexadecyloxypropyl-cidofovir in MRC-5 human lung fibroblasts is explained by unique cellular uptake and metabolism, Molecular Pharmacology, 63:678-681, 2003. 202. Ciesla, S.L., Trahan, J., Winegarden, K.L., Aldern, K.A., Painter, G.R. and Hostetler, K.Y., Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney, Antiviral Research 59: 163-171, 2003. 203. E. R. Kern, K. A. Keith, D. C. Quenelle, D. J. Collins, B. P. Herrod, J. R. Beadle, W. B. Wan, K. Y. Hostetler; Orally Active Alkoxyalkyl Cidofovir Prodrugs for Treatment of Orthopoxvirus Infections, ASM Biodefense Research Conference, March 9-12, 2003, Baltimore, Maryland. 204. R.M.L. Buller, G. Owens, J. Schriewer, J.R. Beadle and K.Y. Hostetler, Efficacy of oral active ether lipid analogs of cidofovir on mortality and tissue viral titers in a lethal ectromelia virus challenge model, Antiviral Research, 62(2), 131, A79, 2003. 16 205. Mucker, E.M., R.O. Baker, J.R. Beadle, J. Shamblin, D. Kefauver, S.H. Zwiers, M. Martinez, S. Ciesla, J. Trahan, K.Y. Hostetler and J.W. Huggins, Orally bioavailable alkoxyalkyl esters of cidofovir: in vitro and in vivo efficacy against orthopox viruses, Proc. 16th International Conference on Antiviral Research, Late breaker #6, Savannah, GA, April 2003. 206. Valiaeva, N. K.A. Keith, K.A. Aldern, J.R. Beadle, E.R. Kern and K.Y. Hostetler, Effects of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG), hexadecyloxypropyl-PMEG and octadecyloxyethyl-OPMEG on replication of HIV-1, herpesviruses and poxviruses, in vitro, Antiviral Research, 62(2), 111, A72, 2003. 207. Aldern, K.A., J.R. Beadle, S.M. Rostami, C. Hartline, E.R. Kern and K.Y. Hostetler, Alkoxyalkyl esters of adefovir: antiviral activity against cytomegalovirus and HIV-1, in vitro, Antiviral Research, 62(2), 101, A69, 2003. 208. Trahan, J., S.L. Ciesla, K.L. Winegarden and K.Y. Hostetler, Oral pharmacokinetics and tissue distribution of 1-O-hexadecyloxypropyl-[2-14C]cyclic cidofovir in mice, Antiviral Research, 62(2), 132, A79, 2003. 209. Ciesla, S.L., W.B. Wan, K.A. Aldern, J.R. Beadle and K.Y. Hostetler, Synthesis of alkoxyalkyl esters of (S)-HPMPA and antiviral activity against herpesviruses, in vitro, Antiviral Research, 62(2), 102, A70, 2003. 210. Keith, K.A., W.B. Wan, S.L. Ciesla, J.R. Beadle, K.Y. Hostetler and E.R. Kern, Inhibitory effect of alkoxyalkyl esters of acyclic nucleoside phosphonates against orthopoxvirus replication, Antiviral Research, 62(2), 110, A72, 2003. 211. Smee, D.F., M.-H. Wong, K.W. Bailey, J.R. Beadle, K.Y. Hosteler, and R.W. Sidwell, Effects of highly active antiviral substances on lethal vaccinia virus (IDH strain) respiratory infections in mice, Int. J. Antimicrobial Agents, 23(5):430-437, 2004 212. Quenelle, D.C., D.J. Collins, K.Y. Hostetler, J.R. Beadle, W.B. Wan and E.R. Kern, Oral treatment of cowpox and vaccinia infections in mice with ether lipid esters of cidofovir, Antimicrobial Agents Chemotherapy, 48:404-412, 2004. 213. Buller, R.M, Owens, G, Schriewer, J, Melman, L, Beadle JR and Hostetler, KY, Efficacy of oral active ether lipid analogs of cidofovir in a lethal mousepox model, Virology, 318(2):474-81, 2004. 214. Keith, KA, Wan, WB, Ciesla, SL, Beadle, JR, Hostetler, KY and Kern, ER. Inhibitory activity of alkoxyalkyl and alkyl esters of cidofovir and cyclic cidofovir against orthopoxvirus replication, in vitro, Antimicrobial Agents Chemotherapy, 48(5):1869-71, 2004. 215. Aldern, K and Hostetler, KY, Cellular Uptake of Cidofovir and Various Alkoxyalkyl Esters of Cidofovir in MRC-5 Cells: Comparison with Antiviral Activity. Antiviral Research, 62(2), 103, A69, 2004. 216. Beadle, JL, Valiaeva, N, Wan, WB, Hostetler, KY, Direct Synthesis of Acyclic Nucleoside Phosphonate Alkoxyalkyl Monoesters. Antiviral Research, 62(2), 98, A66, 2004. 217. Keith, KA, Wan, WB, Beadle, JR, Hostetler, KY, Kern, ER. In Vitro Activity of Alkyl Esters of Cidofovir and Cyclic Cidofovir Against Orthopoxvirus Replication: Comparison of Activity with Alkoxyalkyl Esters. Antiviral Research 62(2), 107, A70, 2004. 218. Hartline, CB, Gustin, KM, Wan, WB, Ciesla, SL, Beadle, JR, Hostetler, KY, Kern, ER., Activity of Ether Lipid Esters of Acyclic Nucleoside Phosphonates Against Adenovirus Replication In Vitro. Antiviral Research, 62(2), 116, A73, 2004. 219. Wan, WB, Hartline, C, Kern, ER, Hostetler, KY, Comparative Antiviral Activity of Alkyl and alkoxyalkyl Esters of Cidofovir Against HCMV Infected Cells, In Vitro. Antiviral Research, 62(2), 71, A55, 2004. 220. Evans, DH, Magee, W, Hostetler, KY, Inhibition of Orthopoxvirus DNA Polymerases by Cidofovir Diphosphate: In Vitro Enzymatic Studies Using Highly Purified Vaccinia Virus DNA Polymerase, Antiviral Research 62(2), 74, A57, May 2004. 17 221. Ruiz, JC, Aldern, KA, Trahan, J, Beadle, JR, Hostetler, KY, Synthesis and Antiviral Activity of 9-[(3-hexadecyl-oxypropyl-phosphono)-1-propyloxymethyl]guanine, Antiviral Research, 62(2), 97, A66, 2004. 222. Trahan, J, Quenelle, DC, Ciesla, SL, Kern, ER, Hostetler, KY, HDP-(S)HPMPA: Oral Pharmacokinetics and Antiviral Activity Against Orthopoxvirus and Murine CMV Infections in Mice, Antiviral Research, 62(2), 108, A71, 2004. 223. Valiaeva, N, Aldern, KA, Trahan, J, Beadle, JR, Hostetler, KY, Synthesis and Antiviral Activity of 5-Substituted Hexadecyloxypropyl-1-[2-(phosphonomethoxy)-ethyl] cytosine (PMEC) Derviatives, Antiviral Research, 62(2), 99, A67, 2004. 224. Bidanset, D.J., Beadle, J.R., Wan, W.B., Hostetler, K.Y. and Kern E.R., Oral activity of ether lipid prodrugs of cidofovir against experimental human cytomegalovirus infections, J. Virology, 190(3):499-503, 2004. 226. Kern, E.R., Collins, D.J., Wan, W.B., Beadle, J.R., Hostetler, K.Y. and Quenelle, D.C., Oral treatment of murine cytomegalovirus infections with ether lipid esters of cidofovir, Antimicrobial Agents Chemotherapy, 48(9):3516-22, 2004. 227. Keith KA, Wan WB, Ciesla SL, Beadle JR, Hostetler KY, Kern ER. Inhibitory activity of alkoxyalkyl and alkyl esters of cidofovir and cyclic cidofovir against orthopoxvirus replication in vitro. Antimicrob Agents Chemother. 48(5):1869-71, 2004. 228. Painter, G.R. and Hostetler, K.Y. Design and development of oral drugs for the prophylaxis and treatment of smallpox infection, Trends in Biotechnology, 22:423-427, 2004. 229. Hartline, C.B., Gustin, K.M., Wan, W.B., Ciesla, S.L. Beadle, J.R., Hostetler, K.Y. and Kern, E.R., Activity of Ether Lipid Ester Prodrugs of Acyclic Nucleoside Phosphonates Against Adenovirus Replication In Vitro, J Infect Dis. 191(3):396-9, 2005. 230. Cheng L, Hostetler KY, Lee J, Koh HJ, Beadle JR, Bessho K, Toyoguchi M, Aldern K, Bovet JM, Freeman WR., Characterization of a Novel Intraocular Drug-Delivery System Using Crystalline Lipid Antiviral Prodrugs of Ganciclovir and Cyclic Cidofovir, Invest Ophthalmol Vis Sci. 2004 Nov;45(11):4138-4144. 231. Wan, W.B., Beadle, J.R., Hartline, C.B., Kern, E.R. , Ciesla, S.L., Valiaeva, N. and Hostetler, K.Y. Comparison of the antiviral activity of alkoxyalkyl and alkyl esters of cidofovir against human and murine cytomegalovirus replication in vitro, Antimicrobial Agents Chemotherapy, 49:656-662,2005. 232. Magee, WC, Hostetler, KY and Evans, DH, Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate, Antmicrobial Agents Chemotherapy, 49:3153-3162, 2005. 233. Lu, S., Cheng, L., Hostetler, K.Y., Koh, H.J., Beadle, J.R., Davidson, M.C. and Freeman, W.R., Intraocular properties of Hexadecyloxypropyl-cyclic-Cidofovir in Guinea Pigs, J. Ocular Pharmacology & Therapeutics, 21:205-209, 2005. 234. Williams-Aziz, S.L., Hartline, C.B., Harden, E.A., Daily, S.M., Prichard, M.N., Kushner, N.L. Beadle, J.R. Wan, W.B., Hostetler, K.Y. and Kern, E.R. Comparative Activity Of Lipid Esters Of Cidofovir And Cyclic Cidofovir Against Replication Of Herpesviruses In Vitro, Antimicrobial Agents & Chemotherapy, 49:3724-3733, 2005. 235. Wu, YK, Cheng, L, Hostetler, KY, Kayikcioglu, O, Valiaeva, N, Beadle, JR, Bergeron-Lynn, G and Freeman, WR, A novel intravitreally injectable, crystalline prodrug of 5-fluorodeoxyuridine (HDP-5FUdR) for sustained intraocular drug delivery to treat pathologic intraocular proliferation, National meeting of ARVO, #471, Miami, 2005. 236. Aldern, KA, Beadle, JR, Wan, WB, Ciesla, SL and Hostetler, KY. Alkoxyalkyl esters of (S)-HPMPA are potent inhibitors of HIV-1 in vitro, Antiviral Res. 65(3):41, A47, 2005. 18 237. Buller, RM, Owens, G, Hostetler, KY and Schriewer, J. Efficacy of smallpox vaccination in the presence of antiviral drugs, cidofovir and hexadecyloxypropyl-cidofovir, Antiviral Res. 65(3):72, A80, 2005. 238. Quenelle, DC, Collins, DJ, Keith, KA, Trahan, J, Beadle, JR, Hostetler, KY and Kern, ER, Effect of oral treatment with HDP-(S)-HPMPA or ODE-(S)-HPMPA on cowpox or vaccinia virus infections in mice, Antiviral Res. 65(3):76, A81, 2005. 239. Ruiz, JC, Beadle, JR, Trahan, J, Aldern, KA, Keith, KA, Hartline, CB, Kern, ER and Hostetler, KY. Synthesis and antiviral activity of alkoxyalkylesters of cidofovir monophosphate, Antiviral Res. 65(3):130, A91, 2005. 240. Choo, H, Beadle, JR, Trahan, J, Aldern, KA and Hostetler, KY. Novel 5-phosphono-pent-2-en-1-yl nucleosides (PPen-Ns) and their alkoxyalkyl phosphonoesters: Synthesis and antiviral evaluation, Antiviral Res. 65(3):132, A91, 2005. 241. Trahan, J, Beadle, JR and Hostetler, KY. Lung targeted antivirals: studies with 1-O-octadecyl-2-O-benzyl-sn-glycero-3-cidofovir, Antiviral Res. 65(3):134, A92, 2005. 242. Andrei, G, van den Oord, J, Hostetler, KY, Beadle, JR, Geypens, D, De Clercq, E and Snoeck, R. Activity of alkoxyalkyl and alkyl esters of (S)-3-hydroxy-2-phosphonylmethoxypropyl derivatives of cytosine (HPMPC) and adenine (HPMPA) and cyclic cidofovir against orthopoxviruses, Antiviral Res. 65(3):136, A92, 2005. 243. Smee DF, Wandersee MK, Bailey KW, Hostetler KY, Holy A, Sidwell RW. Characterization and treatment of cidofovir-resistant vaccinia (WR strain) virus infections in cell culture and in mice. Antiviral Chem Chemother. 16:203-211, 2005. 244. Hostetler, KY Korba BE and Beadle JR, Synthesis and antiviral evaluation of hexadecyloxypropyl-(S)-HPMPA against HBV and drug resistant HBV variants in vitro, Global Antiviral J, 1:Suppl 2, Abst 29, p 31, 2005. 245. C.B. Hartline, E.A. Harden, S.L. Daily, M.P. Johnson, M.N. Prichard, J.R. Beadle, N. Valiaeva, K.Y. Hostetler, and E.R. Kern. Inhibition of Herpesvirus Replication By a Series of Alkoxyalkyl Esters of Purine and Pyrimidine Based Nucleoside Phosphonates, Antiviral Res, abstract, 2006. 246. D.C. Quenelle, D.J. Collins, L.R. Pettway, C.B. Hartline, J.R. Beadle, W.B. Wan, K.Y. Hostetler and E. R. Kern, Effect of Oral Treatment with (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA on Replication of Human Cytomegalovirus (HCMV) or Murine Cytomegalovirus (MCMV) Infection in Animal Models, Antiviral Res. Abstract , 2006. 247. K. A. Aldern, J. R. Beadle, K.Y.Hostetler, Comparison of the Intracellular Metabolism of Cidofovir and (S)-HPMPA and Their Hexadecyloxypropyl Esters, Antiviral Res., Abstract 126, 2006. 248. Nadejda R. Valiaeva, Kathy A. Aldern, Julissa Trahan, James R. Beadle, Karl Y. Hostetler, Alkoxyalkyl esters of phosphonomethoxyethyl purines: Synthesis and antiviral activity against HIV-1, in vitro. Antiviral Res. Abstract 46, 2006. 249. J. Ruiz, J.R. Beadle, J. Trahan, K.A. Aldern, K.A. Keith, J.Schriewer, R.M. Buller, E.R. Kern and K.Y. Hostetler. Metabolic Stability and Antiviral Activity of Novel Branched Methyl Alkoxyalkyl Esters of Cidofovir Against Vaccinia, Cowpox and Ectromelia Infected Cells, in vitro. Antiviral Res. Abstract, 2006. 250. Hostetler KY, Rought, S, Aldern KA, Trahan J, Beadle JR and Corbeil, J. Enhanced Antiproliferative Effects Of Alkoxyalkyl Esters Of Cidofovir In Human Cervical Cancer Cells In Vitro, Mol. Cancer Therap. 5:156-159, 2006. 251. Beadle, J.R., Wan, W.B., Ciesla, S.L., Keith, K.A., Hartline, C., Kern, E.R. and Hostetler,K.Y. Synthesis And Antiviral Evaluation of Alkoxyalkyl Derivatives of 9-(S)-(3-Hydroxy-2-phosphono-methoxypropyl)adenine Against Cytomegalovirus and Orthpoxviruses, in vitro, J. Med. Chem., 49:2010-2015, 2006. 19 252. Randhawa, P, Farasati, NA, Shapiro, R and Hostetler, KY. Ether lipid derivatives of cidofovir inhibit polyomavirus BK replication in vitro, Antimicrob. Agents Chemother. 50:1564-1566, 2006. 253. Hostetler, K.Y., Synthesis and antiviral evaluation of broad spectrum, orally active analogs of cidofovir and other acyclic nucleoside phosphonates, in Advances in Antiviral Drug Design, E. De Clercq, ed., Vol. 5, pp 169-186, 2007. 254. Hostetler, K.Y., K.A. Aldern, W.B. Wan, S.L. Ciesla and J.R. Beadle, Alkoxyalkyl esters of (S)-HPMPA are potent inhibitors of HIV-1 replication, in vitro, Antimicrob. Agents Chemother., 50:2857-2859, 2006 255. Ruiz, J.C., Aldern, K.A., Beadle, J.R., Hartline, C.B., Kern, E.R. and Hostetler, K.Y. Synthesis and antiviral evaluation of alkoxyalkyl esters of phosphonopropoxymethyl-guanine and phosphonopropoxymethyl-diaminopurine, Antiviral Chem. Chemother.,17:89-95, 2006. 256. Valiaeva, N. Beadle, J.R., Aldern, K.A., Trahan, J., and Hostetler, K.Y. Synthesis and antiviral evaluation of alkoxyalkyl esters of acyclic purine and pyrimidine nucleoside phosphonates against HIV-1 in vitro, Antiviral Res.,72:10-19, 2006. 257. I. Lebeau, G. Andrei, F. Dal Pozzo, J.R. Beadle, K.Y. Hostetler, E. De Clercq, J. van den Oord and R. Snoeck, Activity of alkoxyalkyl esters of CDV, cCDV and HPMPA against orthopox- and parapoxviruses in cell monolayers and in organotypic cultures, Antimicrob. Agents Chemotherap. 50(7):2525-9, 2006. 258. A.M. Tammewar, AM, Cheng, L., Hostetler, K.Y., Falkenstein, I., Beadle, J.R., Kozak, I., Freeman, W.R., Intraocular Properties In Rabbit Eyes Of Hexadecyloxy-propyl-Cyclic-HPMPA, A Potent Crystalline Anti CMV Lipid Prodrug of HPMPA. National meeting of the Association for Research Vision and Opthalmology (ARVO), Miami, 2006. 259. Kornbluth, R.S., Smee, D.F., Sidwell, R.W., Snarsky, V., Evans, D.H. and Hostetler, K.Y. Mutations in the E9L Polymerase Gene of Cidofovir Resistant Vaccine WR are Responsible for the Drug-Resistant Phenotype, Antimicrob. Agents Chemother. 50:4038-4043, 2006. 260. Hostetler, K.Y., Painter, G.R., Almond, M.R., Trost, L.C., Lampert, B.M., Aldern, K.A. and Beadle, J.R. In vitro and in vivo evaluation of hexadecyloxypropyl 9-(R)-[2-(phosphono-methoxy)propyl]-adenine as a potential treatment of HIV-1 infections, Frontiers in Drug Development for Antiretroviral Therapies, Cancun Mexico, December 10-14, 2006; Global Antiviral J. 2:Suppl 2, Abst 84, p 96, 2006. 261. Choo H, Beadle JR, Chong Y, Trahan J, Hostetler KY. Synthesis of the 5-phosphono-pent-2-en-1-yl nucleosides: A new class of antiviral acyclic nucleoside phosphonates. Bioorg Med Chem. 15:1771-1779, 2007. 262. Choo, H., Beadle, J.R., Kern, E.R., Prichard, M.N., Keith, K.A., Hartline, C.B., Trahan, J., Aldern, K.A., Korba, B.E. and Hostetler, K.Y., Antiviral activities of novel 5-phosphono-pent-2-en-1-yl nucleosides and their alkoxyalkyl phosphonoesters, Antimicrob. Agents Chemother. 51:611-615, 2007. 263. Beadle JR, Hostetler KY, Buller RM, Schriewer J, Aldern KA, Prichard MN, Keith K and Kern ER, Synthesis and antiviral evaluation of iso-methyl-alkoxyalkyl (S)-HPMPA esters, Antiviral Res. 74 (3): abstract 51, p A48, 2007 264. Morrey JD, Beadle JR and Hostetler KY, Effect of oral HDP-(S)-HPMPA or adefovir dipivoxil on hepatitis B virus in transgenic mice, Antiviral Res, 74(3), Late breaker abstract, LB-8, 2007. 265. Andrei G, Snoeck R, Neyts J, De Clercq E, Valiaeva N, Beadle J and Hostetler KY, Enhanced antiviral activity of hexadecyloxypropyl-PME-N6-cyclopropyl-DAP against herpesviruses hepatitis B virus and vaccinia virus in vitro, Antiviral Res. 74 (3): abstract 118, p A76, 2007 266. Aldern KA, Beadle JR, Trahan, J and Hostetler KY, Uptake and metabolism of cidofovir and oleoyloxyethyl ethyl cidofovir in human papillomavirus positive ME-180 human cervical cancer cells, Antiviral Res. 74 (3): abstract 137, p A83, 2007 267. Hostetler, K.Y., Beadle, J.R., Trahan, J., Aldern, K.A., Owens, G., Schriewer, J. Melman, L, and Buller, R.M. Oral 1-O-octadecyl-2-O-benzyl-sn-glycero-3-cidofovir targets the lung and is effective against a lethal respiratory challenge with ectromelia virus in mice, Antiviral Res. 73:212-218, 2007. 268. Dal Pozzo, F., Andrei, G., Lebeau, I., Beadle, J.R., Hostetler, K.Y., De Clercq, E. and Snoeck, R. In Vitro Evaluation Of The Anti-Orf Virus Activity Of Alkoxyalkyl Esters Of CDV, cCDV And (S)-HPMPA, Antiviral Res.,75:52-57, 2007. 269. Ruiz, J.C., Beadle, J.R., Aldern, K.A., Keith, K.A., Hartline, C.B., Kern, E.R. and Hostetler, K.Y. Synthesis and antiviral evaluation of alkoxyalkyl phosphate conjugates of cidofovir and adefovir, Antiviral Res., 75:87-90, 2007. 270. Painter, G.R., M.R. Almond, L.C. Trost, B.M. Lampert, J. Neyts, E. De Clercq, B.E. Korba, K.A. Aldern, J.R. Beadle and K.Y. Hostetler, Evaluation of hexadecyloxypropyl-9-R-[2-(phosphonomethoxy)propyl]adenine, CMX157, a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections, Antimicrob. Agents Chemother. 51:3505-9, 2007. 271. Quenelle, D.C., D.J. Collins, B.P. Herrod, K.A. Keith, J. Trahan, J.R. Beadle, K.Y. Hostetler and E.R. Kern, Effect of oral treatment with hexadecyloxypropyl-[(S)-9-(3-hydroxy-2-phosphonylmethoxy-propyl)adenine] [(S)-HPMPA] or octadecyloxyethyl-(S)-HPMPA on cowpox or vaccinia virus infections in mice, Antimicrob. Agents Chemother., 51:3940-3947, 2007. 272. Magee, W.C., K.A. Aldern, K.Y. Hostetler and D.H. Evans, Cidofovir and (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine are highly effective inhibitors of vaccinia virus DNA polymerase when incorporated into the template strand, Antimicrob. Agents Chemother. 52:586-597, 2008. 273. Randhawa P, Zemlicka J, Sauerbrei A, Meier C, Hostetler KY, Beadle JR, Farasati NA, Huang Y, Bradley M. Anti-BK virus activity of nucleoside analogs, Antimicrob Agents Chemother. 52:1519-1521, 2008. 274. Quenelle, D.C., D.J. Collins, L.R. Pettway, C.B. Hartline, J.R. Beadle, W.B. Wan, K.Y. Hostetler and E.R. Kern, Effect of oral treatment with (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA on replication of murine cytomegalovirus or human cytomegalovirus in animal models, Antiviral Res., 79:133-5, 2008. 275. Wyles DL, Schooley RT, Kaihara KA, Beadle JR and Hostetler KY, Anti-hepatitis C virus replicon activity of alkoxyalkyl esters of (S)-HPMPA and other acyclic nucleoside phosphonates, Antiviral Res. 78:A21, Abstract 15, 2008. 276. Magee W, Hostetler KY and Evans D, Vaccinia DNA polymerase is profoundly inhibited by cidofovir and (S)-HPMPA incorporated into the template strand, Antiviral Res. 78:A30, Abstract 36, 2008 277. Bravo F, Cardin R, Hostetler K and Bernstein D, Effect of treatment with the cidofovir analog HDP-CDV in guinea pig models of cytomegalovirus infection, Antiviral Res. 78:A31, Abstract 39, 2008. 278. Valiaeva N, Aldern KA, Trahan J, Beadle JR, Hostetler KY, Synthesis and evaluation of octadecyloxyethyl esters of five 3-hydroxy-2-(phosphonomethoxy)propyl nucleoside phosphonates in HIV-1 infected cells, Antiviral Res. 78:A49, Abstract 86, 2008 279. Prichard MN, Hartline CB, Harden EA, Daily SL, Beadle JR, Valiaeva N, Kern ER, and Hostetler KY, Inhibition of Herpesvirus Replication by Hexadecyloxypropyl Esters of Purine and Pyrimidine Based Phosphonomethoxyethyl Nucleoside Phosphonates, Antimicrob. Agents Chemother. 52:4326-4330, 2008. 280. Magee, W.C., Hostetler, K.Y. and Evans, D.H. The effects of cidofovir diphosphate and HPMPA diphosphate on retrovirus reverse transcriptases. Am. Society of Virology, 2009. 281. Trahan, J, Aldern, K.A. and Hostetler, K.Y. Inhibition of the growth of human papilloma positive Me-180 human cervical carcinoma tumors by 1-O-octadecyloxethyl-phoshonomethoxyethyl-guanine (ODE-PMEG) in athymic nude mice, Antiviral Res. 82:A42, Abstract 85, 2009. 282. Valiaeva, N., Trahan, J., Keith, K.A., Hartline, C., Prichard, M.N., Beadle, J.R. and Hostetler, K.Y. Evaluation of octadecyloxyethyl esters of 3-hydroxy-2-(phosphonomethoxy)propyl nucleosides against HCMV, HSV and Poxviruses, Antiviral Res. 82:A52, Abstract 115, 2009. 283. Roth, J.P., McLean, T.Z., Valiaeva, N., Beadle, J.R., Hostetler, K.Y. and Barnard, D.L. Antiviral activity of octadecyloxypropyl esters of 3-hydroxy-2-(phosphonomethoxy)propyl nucleosides against adenoviruses in vitro, Antiviral Res., 82:A41, Abstract 83, 2009. 284. Hostetler KY, Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art, Anviral Res., 82:A84-98, 2009. 285. Wyles DL, Kaihara KA, Korba BE, Schooley RT, Beadle JR and Hostetler, KY., ODE-(S)-HPMPA Is A Potent And Selective Inhibitor Of Hepatitis C Virus Replication In Genotype 1a, 1b And 2a Replicons, Antimicrob. Agents Chemother. 53(6):2660-2662, 2009. 286. Morrey JD, Korba BE, Beadle JR, Wyles DL and Hostetler KY., Alkoxyalkyl Esters of (S)-HPMPA Are Potent and Selective Inhibitors of Hepatitis B Virus Replication in Vitro and in Transgenic Hepatitis B Mice in vivo, Antimicrob. Agents Chemother. 53(7):2865-70, 2009. 287. Valiaeva, N., Prichard, M.N., Buller, R.M., Beadle, J.R., Hartline, C.B., Schriewer, J., Trahan, J. and Hostetler, K.Y. Antiviral Evaluation of Octadecyloxyethyl Esters of (S)-3-Hydroxy-2-phosphonomethoxy)propyl Nucleosides Against Herpesviruses and Orthopoxviruses, Antiviral Res, 84(3):254-9, 2009. 288. Botros, S.S., William, S., Beadle, J.R., Valiaeva, N. and Hostetler, K.Y., Antischistosomal activity of hexadecyloxypropyl cyclic HPMPA and other alkoxyalkyl esters of acyclic nucleoside phosphonates assessed by schistosome worm killing in vitro, Antimicrob. Agents Chemother. 53(12):5284-7, 2009. 289. Valiaeva, N., Trahan, J., Aldern, K.A., Beadle, J.R. and Hostetler, K.Y. Antiproliferative effects of octadecyloxyethyl 9-[2-(phosphonomethoxy)ethyl]guanine against Me-180 human cervical cancer cells in vitro and in vivo, Chemotherapy, 56:54-59, 2010. 290. Aldern KA, Trahan J, Beadle JR, Su Y, Hostetler KY. Oral pharmacokinetics of hexadecyloxypropyl 9-(R)-[2-(phosphonomethoxy)propyl]guanine (HDP-(R)-PMPG) in mice using LC/MS/MS, Antiviral Res. 86:A51, #114, 2010. 291. Beadle JR, Chatterjee S, Magee WC, Sykes BD, Evans DH, Hostetler KY. Synthesis and solution structure of DNA complexes containing the potent antipoxvirus agent cidofovir, Antiviral Res. 86:A52, #117, 2010. 292. Ruiz JC, Aldern KA, Trahan J, Beadle JR, Hostetler KY. Synthesis and antiviral evaluation of alkoxyalkyl esters of 9-(R)-[2-(phosphonomethoxy)propyl] nucleosides, Antiviral Res. 86:A66, #157, 2010. 293. Trahan J, Valiaeva N, Beadle JR, Hostetler KY. Acute toxicity of oral octadecyloxyethyl esters of 3-hyxroxy-2-(phosphonomethoxy)propyl nucleosides in Balb/c mice, Antiviral Res. 86:A68, #163, 2010. 294. Valiaeva N, Beadle JR, Wyles DL, Schooley RT, Hostetler, KY. Octadecyloxyethyl 9-(S)-[3-methoxy-2-(phosphonomethoxy)propyl]adenine: A novel alkoxyalkyl acyclic nucleoside analog with anti-HCV activity and reduced toxicity, Proceedings of the 23rd International Conference on Antiviral Research, San Francisco CA, April 25-28, 2010, Late Breaker #L-6. 22
295. Julien O, Beadle JR, Chatterjee S, Magee WC, Hostetler KY, Evans DH, Sykes BD. Solution structure of a DNA
duplex containing the potent antipoxvirus agent cidofovir, 24th Int. Conf on Magnetic Resonance in Biological Systems
(ICMRBS), Cairns, Australia, August 22-27, 2010.
296. Hostetler KY. Synthesis and early development of hexadecyloxypropyl-cidofovir: an oral antipoxvirus nucleoside
phosphonate, Viruses. 2: 2213-2225, 2010.
297. Bravo FJ, Bernstein DI, Beadle JR, Hostetler KY, Cardin RD. Oral hexadecyloxypropyl-cidofovir therapy in pregnant
guinea pigs improves outcome in the congenital model of cytomegalovirus infection. Antimicrob Agents Chemother.2011
Jan;55(1):35-41. Epub 2010 Nov 15. PubMed PMID: 21078944; PubMed Central PMCID: PMC3019685.
298. Cheng L, Hostetler K, Valiaeva N, Tammewar A, Freeman WR, Beadle J, Bartsch
DU, Aldern K, Falkenstein I. Intravitreal crystalline drug delivery for intraocular proliferation diseases. Invest Ophthalmol
Vis Sci. 2010 Jan;51(1):474-81. Epub 2009 Aug 20. PubMed PMID: 19696179; PubMed Central PMCID: PMC2869063.
299. Julien O, Beadle JR, Magee WC, Chatterjee S, Hostetler KY, Evans DH, Sykes BD. Solution structure of a DNA
duplex containing the potent anti-poxvirus agent cidofovir. J Am Chem Soc. 2011 Feb 23;133(7):2264-74. Epub 2011 Jan
31. PubMed PMID: 21280608.
300. Li Y, Li G, Hou J, Chen H, Hostetler KY, Valiaeva N, Beadle JR, Qu J, Cheng L. Intraocular Toxicity and Inhibition
of Cellular Proliferation by Hexadecyloxypropyl 9-[2-(phosphonomethoxy)ethyl]guanine (HDP-PMEG), submitted for
publication, 2011.
301. Hostetler KY, Magee WC, Evans DH, Valiaeva N, Beadle JR, Aldern KA, Richman DD. 9-(S)-[3-hydroxy-2-
(phosphonomethoxy)propyl] nucleosides: A new mechanism of inhibition of HIV replication, HIV DART: 2010 Frontiers in
Drug Development for Antiretroviral Therapies, Global Antiviral J. 6, Suppl 1, Abst 46, p 43, 2010.
302. Ruiz J, Beadle JR, Buller RM, Schreiwer J, Prichard MN, Keith KA, Lewis KC, Hostetler KY. Synthesis, metabolic
stability and antiviral evaluation of various alkoxyalkyl esters of cidofovir and 9-(S)-[3-hydroxy-2-
(phosphonomethoxy)propyl]adenine, Bioorg Med Chem, 19:2950-2958, 2011.
303. Magee W, Julien O, Beadle JR, Chatterjee S, Hostetler KY, Sykes B, Evans DH. The mechanism of action of the
antiviral agent cidofovir against viral polymerases, ASM Conference Viral Genome Replication, Banff, Alberta, Canada,
February 6-9, 2011.
304. Wyles DL, Jones KA, Valiaeva N, Beadle JR, Hostetler KY, Schooley RT. Continued selection with the acyclic
nucleoside phosphonate Hepatitis C virus (HCV) inhibitor ODE-(S)-MPMPA in vitro results in reversion to wild-type NS5B
and a resistant cell phenotype suggesting a high barrier to resistance, CROI, February 2011. Boston.
305. Hou J, Li Y, Zhou Z, Valiaeva N, Beadle JR, Hostetler KY, Freeman WR, Hu D-N, Chen H, Cheng L. Antiproliferative
property of hexadecyloxypropyl 9-[2-(phosphonomethoxy)ethyl] guanine for unwanted ocular proliferation, Mol Vision,
17:627-637, 2011.
306. Wyles DL, Jones KA, Valiaeva N, Schooley RT, Hostetler KY, ODE-(S)-MPMPA displays potent HCV replicon
suppression for one week after compound removal in cell culture, EASL abstract, Berlin,
2011.

307. Beadle JR, Hostetler KY, Alkoxyalkyl Ester Prodrugs of Antiviral Nucleoside Phosphonates and Phosphonates, in
Antiviral Drug Strategies, 1st Edition, E. De Clercq, Editor, Wiley-VCH Verlag GmbH & Co, KGaA, Weinheim. pp 181-208,
2011.
308. Wyles DL, Jones KA, Valiaeva N, Beadle JR, Schooley RT, Hostetler KY. Enhanced cellular penetration of ODE-(S)-MPMPA accounts for its prolonged post-exposure anti-HCV activity, abstract 146, 24th ICAR, Sofia, Bulgaria, May 2011. 309. Beadle JR, Cheng L, Hostetler KY, Freeman WR, Intravitreal alkoxyalkyl esters of cyclic cidofovir for treatment of ocular viral infections, abstract 13, 24th ICAR, Sofia, Bulgaria, May 2011. 310. Valiaeva N, Beadle JR, Wyles DL, Schooley RT, Hostetler KY, Synthesis and Antiviral Activity of 3-Methoxy-2- (phosphonomethoxy)propyl Nucleoside Esters Against HCV and HIV-1, abstract, 24th ICAR, Sofia, Bulgaria, May 2011. 311. Magee WC, Hazes B, Hostetler KY, Evans DH, The Inhibition of Vaccinia Virus by the Acyclic Nucleoside Phosphonate MPMPA, oral presentation, American Society of Virology, 2011. 312. Magee WC, Valiaeva N, Beadle JR, Hostetler KY, Evans DH, HIV-1 is Inhibited by (S)-9-[3-Hydroxy- (2-Phosphonomethoxy)Propyl] Nucleosides by a Novel Mechanism of Action, submitted, 2011. 313. Valiaeva N, Wyles DL, Schooley RT, Hwu JB, Beadle JR, Prichard MN, Hostetler KY. Synthesis and antiviral evaluation of 9-(S)-[3-Alkoxy-2-(phosphonomethoxy)propyl] nucleoside alkoxyalkyl esters: inhibitors of hepatitis C virus
and HIV-1 replication, submitted, 2011.
ISSUED PATENTS

1. Hostetler, K.Y. and Deftos, L.J., U.S. Patent #4,692,433, "Method and composition for regulating calcium and
skeletal metabolism of mammals," September 8, 1987.
2. Deftos, L.J. and Hostetler, K.Y., U.S. Patent #4,837,380, "Liposome-calcitonin preparation," June 6, 1989.
3. Basava, C. and Hostetler, K.Y. U.S. Patent #5,175,146, "Synthetic calcitonin peptides," December 29, 1992.
4. Hostetler, K.Y. and Kumar, R. U.S. Patent #5,194,654, "Lipid derivatives of phosphonoacids for liposomal
incorporation and method of use," March 16, 1993.
5. Hostetler, K.Y., Kumar, R., and Stuhmiller, L.M., U.S. Patent #5,223,263, "Liponucleotide-containing liposomes," June
29, 1993.
6. Basava, C. and Hostetler, K.Y., U.S. Patent #5,364,840, "Synthetic Calcitonin Peptides," November 15, 1994.
7. Hostetler, K.Y. and Kumar, R., U.S. Patent #5,411,947, "Method of converting a drug to an orally available form by
covalently bonding a lipid to the drug," May 2, 1995.
8. Hostetler, K.Y. and Kumar, R., U.S. Patent #5,463,092, “Lipid Derivatives of Phosphonoacids for Liposomal
Incorporation and Method of Use,” October 31, 1995.
9. Hostetler, K.Y. and Sridhar, C.N., U.S. Patent #5,484,809, "Prodrugs for Oral Administration Containing Taxol or
Substituted Taxol Covalently Bound to a Phospholipid," January 16, 1996.
10. Basava, C. and Hostetler, K.Y., U.S. Patent #5,554,728, “Lipid Conjugates of Therapeutic Peptides and Protease
Inhibitors,” September 10, 1996.
11. Hostetler, K.Y., U.S. Patent #5,580,571, “Nucleoside Analogues,” December 3, 1996.
12. Hostetler, K.Y., U.S. Patent #5,654,286, “Nucleotides for Topical Treatment of Psoriasis, and Methods for Using Same,” August 5, 1997. 13. Hostetler, K.Y. and Kini, G.D., U.S. Patent 5,696,277, “Antiviral Prodrugs,” December 9, 1997. 14. Hostetler, K.Y. and kumar, R., U.S. Patent 5,744,41, “Lipid derivatives of phosphonoacids for liposomal incorporation and methods of use,” April 28, 1988. 15. Hostetler, K.Y., Kumar, R. and Sridhar, N.C., U.S. Patent 5,744,592, “Lipid prodrugs for oral administration, April 28, 1998. 16. Hostetler, K.Y., U.S. Patent 5,756,116, “Nucleoside phosphate therapy for viral infection,” May 26, 1998. 17. Van den Bosch, H., van Wijk, G.M.T., Kumar, R. and Hostetler, K.Y., U.S. Patent 5,780,617, “Synthesis of liponucleotides,” July 14, 1998. 18. Basava, C. and Hostetler, K.Y., US Patent #5,804,552, “Lipid conjugates of therapeutic peptides and protease inhibitors,” September 8, 1998. 19. Hostetler, K.Y., U.S. Patent #5,817,638, “Antiviral liponucleosides: Treatment of hepatitis B”, October 6, 1998. 20. Hostetler, K.Y., Kumar, R. and Sridhar, N.C., U.S. Patent #5,827,831, “Lipid nucleotide analog prodrugs for oral administration”, October 27, 1998. 21. Hostetler, K.Y., U.S. Patent #5,879,700, “Nucleotide analog phosphates for topical use,” March 9, 1999 22. Hostetler, K.Y. and Kini, G.D., US Patent #6,002,029, “Antiviral prodrugs,” December 14, 1999. 23. Hostetler, K.Y. US Patent #6,015,573, “Nucleoside phosphate therapy for infection”, January 15, 2000. 24. Hostetler, K.Y., European Patent #EP 0350287 B1, “Lipid derivatives of antiviral nucleosides, liposomal incorporation and method of use,” September 9, 2000. 25. Hostetler, K.Y., U.S. Patent #6,252,060, “Antiviral liponucleosides: treatment of hepatitis B, June 26, 2001. 26. Hostetler, K.Y. and Kumar, R., European Patent #EP 0674646 B1, “Lipid derivatives of phosphonoacids for liposomal incorporation and method of use,” April 10, 2001. 27. Hostetler, K.Y., Kumar, R. and Stuhmiller, L.M., U.S. Patent #6,448,392B, “Lipid derivatives of antiviral nucleosides: liposomal incorporation and method of use”, September 10, 2002. 28. Hostetler, K.Y., Kumar, R. and Stuhmiller, L.M., U.S. Patent #6,599,887B2, “Methods of treating viral infections using antiviral liponucleotides”, July 29, 2003. 29. Rosowsky, A., Hostetler, K.Y., Beadle, J.R., and Richman, D.R., U.S. Patent #6,686,462, “Antiviral compounds and methods of administration”, February, 4, 2004. 30. Hostetler, K.Y., Beadle, J.R. and Kini, G.D., U.S. Patent #6,716,825, “Phosphonate Compounds,” April 6, 2004. 31. Hostetler, K.Y., Beadle, J.R. and Kini, G.D., U.S. Patent #7,034,014, “Phosphonate Compounds,” April 25, 2006. 32. Hostetler, K.Y., Beadle, J.R. and Kini, G.D., U.S. Patent #7,044,772, “Phosphonate Compounds,” August 22, 2006. 25 33. Hostetler, K.Y., Beadle, J.R. and Kini, G.D., U.S. Patent #7,098,197, “Phosphonate Compounds,” August 29, 2006. 34. Hostetler, K.Y., Beadle, J.R. and Kini, G.D., U.S. Patent #7,452,898, “Phosphonate Compounds,” November 18, 2008. 35. Hostetler, K.Y., Kini, G.D. and Beadle, J.R., U.S. Patent #7,517,858, “Prodrugs of pharmaceuticals with improved bioavailability”, April 14, 2009. 36. Hostetler KY and Wan WB. US Patent #7,652,001 B2, “Pharmacologically active agents containing esterified phosphonates and methods for use thereof”, January 26, 2010. 37. Hostetler, K.Y., Beadle, J.R. and Kini, G.D., U.S. Patent #7,687,480 B2, “Phosphonate Compounds,” March 30, 2010. 38. Hostetler, K.Y., Beadle, J.R., Ruiz, J., Almond, M.R., Painter, G.R., Riley, T.A. Francom, P., U.S. Patent #7,749,983, “Metabolically stable alkoxyalkyl esters of antiviral or antiproliferative phosphonates, nucleoside phosphonates and nucleoside phosphates, July 6, 2010. 39. Hostetler, K.Y., Beadle, J.R. and Kini, G.D., U.S. Patent #7,790,703 B2, “Phosphonate Compounds,” September 7, 2010.

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Appendix B: Folic Acid and the Prevention of Neural Tube Defects Neural Tube Defects Neural tube defects (spina bifida, anencephaly and encephalocoele) are a major group of serious birth defects. The abnormality occurs when the spinal cord and brain are forming during the fourth week after conception (in the sixth week after the last normal menstrual period). Over 95% of neural tube defe

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