Drug discovery: Past, present and future

Progress in Drug Research

Volumn 50, Issue , 1998, Pages 9-105

  Kaul, Pushkar N ^a,b,c,d  

^a CLARK ATLANTA UNIVERSITY   (United States)

^b Banaras University   (India)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d HARVARD UNIVERSITY   (United States)

Author keywords

Autotherapeutics; Bioinformatics; Biotherapeutics; Combinatorial chemistry; Drug discovery; Gene therapy; Marine toxins; Molecular graphics; Molecular modeling; Oligonucleotides; Prions

Indexed keywords

ALKALOID; AYURVEDIC DRUG; CHLORPROMAZINE; CLONIDINE; CYCLOSPORIN; DEPSIPEPTIDE; ENZYME; ENZYME INHIBITOR; FUROSEMIDE; HORMONE; INDOLE ALKALOID; IONOPHORE; LEVODOPA; MACROLIDE; MARINE TOXIN; MICROBIAL PRODUCTS NOT CLASSIFIED ELSEWHERE; MORPHINE; NATURAL PRODUCT; NEUROTRANSMITTER; OLIGONUCLEOTIDE; PACLITAXEL; PHOSPHOROTHIOIC ACID DERIVATIVE; PLANT PRODUCTS NOT CLASSIFIED ELSEWHERE; PODOPHYLLIN; RECEPTOR; RECOMBINANT DNA; SANFETRINEM; SANFETRINEM CILEXETIL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL; ZILEUTON;

BIOENGINEERING; CHEMISTRY; CLINICAL TRIAL; COMPUTER; FEEDBACK SYSTEM; GENE; GENE SWITCHING; GENE THERAPY; HUMAN; HYPERTENSION; INFORMATION SCIENCE; MEDICAL GENETICS; MOLECULAR BIOLOGY; MOLECULAR CLONING; MOLECULAR DYNAMICS; MOLECULAR MODEL; MOLECULAR RECOGNITION; NONHUMAN; PARKINSON DISEASE; PRION; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RECEPTOR AFFINITY; REVIEW; ROBOTICS;

EID: 0031865508     PISSN: 0071786X     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-0348-8833-2_1     Document Type: Review

References (397)

1. J. Watson, J.A. Barondess and S. Lock, eds.: The Oxford Medical Companion, Oxford Univ. Press, Oxford 1994, p. 586.
2. P.N. Kaul: Progr. Drug Res. 47, 151 (1996).
3. L. Chang-Xiao: J. Ethnopharmacol. 19, 119 (1987).
4. K. Walker: The Story of Medicine, Oxford Univ. Press, New York 1955.
5. W.E. Court: Tr. Pharmacol. Sci. 6, 225 (1985).
6. National Geographic Magazine, December 1972.
7. P.N. Kaul and R.K. Kaul: Contributions of American Indian Medicine to Modern Medicine (in preparation).
8. F.N.L. Poynter and K.D. Keele: A Short History of Medicine, Mills & Boon, London 1961.
9. P. Ehrlich and K. Shiga: Klin. Wochenschr. 41, 329 (1904).
10. U.S. Patent 986, 148 (1911), P. Ehrlich and A. Bertheim, Farbwerke Hoechst, AG.
11. H. Erlenmeyer and M. Leo: Helv. Chim. Acta 15, 117 (1932).
12. A. Burger, in: E. Jucker (ed.), Progr. Drug Res. 37, 287 (1981).
13. R. Reiner: Antibiotics, Gary-Thieme Verlag, Stuttgart 1982.
14. J.E. Conte, Jr.: Manual of Antibiotics and Infectious Diseases, 8th edit., Williams Wilkins, Baltimore 1995.
15. A. der Marderosian: J. Pharm. Sci. 58, 1 (1969).
16. P.N. Kaul: Pure and Appl. Chem. 54, 1963 (1982).
17. P.N. Kaul and P. Daftari: Annu. Rev. Pharmacol. Toxicol. 26, 117 (1986).
18. P.N. Kaul: Progr. Drug Res. 35, 521 (1990).
19. G.M. Konig: Dtsch-Apoth-Ztg. 132 (April 2), 673 (1992).
20. M. Chr. Krebs: Fortschr. Chem. Organ. Naturstoffe 48, 151 (1986).
21. J.P. Swazey: Chlorpromazine in Psychiatry, A Study of Therapeutic Innovation, M.I.T. Press, Cambridge 1974.
22. M. Wolf and H. Morr: Imidazoline - New Facts of a Cinderella Molecule, in: F.G. McMahon (ed.), Future Trends in Therapeutics, Future Publishing Co., New York 1978, pp. 179-189.
23. M. Pigini, P. Bousquet, A. Carotti, M. Dontenwill, M. Gianella, R. Moriconi, A. Piergentili, W. Quaglia, S.K. Tayebati and L. Brazili: Bioorganic & Medicinal Chemistry 5, 833 (1997).
24. S. Regunathan and D.J. Reis: Annu. Rev. Pharmacol. Toxicol. 36, 511 (1996).
25. K.H. Beyer: Discovery, Development and Delivery of New Drugs, Spectrum Publication, New York 1978.
26. A. Bertler and E. Rosengren: Experientia 15, 10 (1959).
27. A. Carlson: Nature 180, 1200 (1959).
28. G.C. Cotzias, M.H. van Woort and L.M. Schifler: N. Engl. J. Med. 276, 74 (1967).
29. J.M. Cederbaum: Clin. Pharmacokinet. 13, 141 (1987).
30. V.G. Vernier: Antiparkinsonism Drugs, in: M.E. Wolff (ed.), Burger's Medicinal Chemistry and Drug Discovery, vol. 1, Wiley-Interscience, New York 1996.
31. H. Singh, in: J.J. Stezowski, J.L. Huang and M.C. Shao (eds.), Molecular Structure: Chemical Reactivity and Biological Activity, Oxford Univ. Press, Oxford 1988.
32. E.R. Kandal, J.H. Schwartz and T.M. Jessell: Principles of Neural Science, 3rd edit., Elsevier, New York 1991.
33. E. Rodriguez and R. Wrangham, in: K.R. Downum, J.T. Romeo and H.A. Stafford (eds.), Phytochemical Potential of Tropical Plants, Plenum Press, New York 1993, pp. 89-105.
34. A. Burger, ed.: Medicinal Chemistry, 3rd edit., Wiley-Interscience, New York 1970, p. 1065.
35. A. Stoll and W. Kreis: Helv. Chim. Acta 16, 1049, 1390 (1933).
36. R.B. Turner: Chem. Rev. 43, 1 (1948).
37. R. Reichstein: Angew. Chem. 63, 412 (1951).
38. C. Tamm: Progr. Org. Chem. Natural Products 14, 71 (1957).
39. A.H. Beckett and A.F. Casy: J. Pharm. Pharmacol. 6, 986 (1954).
40. E. Mutschler, H. Derendorf, M. Schaefer-Kortinig, K. Elrod and K.S. Estes: Drug Actions, CRC Press, Ann Arbor 1995, pp. 155-160.
41. T. Amann and M.H. Zenk: Tetrahedron Lett. 32 (30), 3675 (1991).
42. M.C. Sanguineti and R.S. Cass: Circ. Res. 55, 336 (1984).
43. A.C. Sartorelli and W.A. Creasy: Annu. Rev. Pharmacol. 9, 51 (1969).
44. E.K. Rowinsky and R.C. Donehower: Pharmacol. Ther. 52, 35 (1991).
45. R.J.A. Aur, J.V. Simone, M.S. Verzosa, H.O. Hustu, L.F. Barker, D.P. Pinkel, G. Rivera, G.V. Dahl, A. Wood, S. Stagner and C. Mason: Cancer 42, 2123 (1978).
46. J.B. Sorensen and H.H. Hansen: Investigational New Drugs 11, 103 (1993).
47. R.C. Donehower and C.K. Rowinsky: Anticancer Drugs from Plants, in: V.T. Devita, S. Hellman and A. Rosenberg (eds.), Cancer, Principle and Practice of Oncology, Lippincott, Philadelphia 1993, pp. 409-417.
48. A. Depierre, E. Lemarie, G. Dabouis, G. Gamier, P. Jacoulet and J.C. Dalphin: Am. J. Clin. Oncol. 14, 115 (1991).
49. I.W. Kaplan: New Orleans Med. Surg. J. 94, 388 (1942).
50. V. Podwyssotzki: Arch. Exp. Pathol. Pharmakol. 13, 29 (1880).
51. J.R. Hartwell and A.W. Schrecker: J. Amer. Chem. Soc. 73, 2909 (1951).
52. H. Emmenegger, H. Staehelin, J. Rutschmann, J. Renz and A. von Wartburg: Arzneimittel Forsch. 11, 327, 459 (1961).
53. H. Staehelin and A. von Wartburg, in: E. Jucker (ed.): Progr. Drug Res. 33, 169 (1989).
54. C. Keller-Justen, M. Kuhn, A. von Wartburg and H. Staehelin: J. Med. Chem. 14, 936 (1971).
55. N.-F. Billups and S.M. Billups (eds.): American Drug Index, Facts and Comparisons, St. Louis 1997.
56. T. Bryan-Brown: Quart. J. Pharm. Pharmacol. 5, 205 (1932).
57. A.D. Bus and A.D. Waigh, in: M.E. Wolff (ed.): Berger's Medicinal Chemistry and Drug Discovery, 5th edit., Wiley-Interscience, New York 1995, p. 997.
58. E.K. Rowinsky, N. Onetto, R.M. Canetta and S.G. Arbuck: Sem. Oncol. 19, 646 (1992).
59. M. Suffness, in: J.A. Bristol (ed.): Annu. Reports in Med. Chem. 28, 305 (1993).
60. P.B. Schiff, J. Fant and S.B. Horwitz: Nature 277, 665 (1979).
61. S. Rao, N.E. Krauss, J.M. Heerding, C.S. Swindell, I. Ringel, G.A. Orr and S. B. Horwitz: J. Biol. Chem. 269, 3132 (1994).
62. M.A. Jordan, K. Wendell, S. Gardiner, W.B. Derry, H. Copp and L. Wilson: Cancer Res. 56, 816 (1996).
63. S. Haldar, J. Chintapalli, C.M. Croce : Cancer Res. 56, 1253 (1996).
64. C. Palomo, A. Arrieta, F.P. Cossio, J.M. Aizpurna, A. Mielgo and N. Aurrekoe: Tetrahedron Lett. 31, 6429 (1990).
65. E.K. Rowinsky: Annu. Rev. Med. 48, 353 (1997).
66. J.C. Sheehan: Advances in Chemistry Series No. 45, Amer. Chem. Soc., Washington D.C. 1964, pp. 15-24.
67. W. Sneader: Drug Discovery: The Evolution of Modern Medicine, John Wiley, New York 1989, pp. 321-324.
68. R. Gordee and M. Depono: Drugs of the Future 14, 939 (1989).
69. J.S. Glasby: Encyclopedia of Antibiotics, John Wiley & Sons, London 1976.
70. G. Lancini, F. Parenti and G.G. Gallo: Antibiotics: A Multidisciplinary Approach, Plenum Press, New York 1995.
71. P.N. Kaul: Impact Sci. on Soc. 29, 123 (1979).
72. N.J. de Souza, B.N. Ganguli and J. Reden: Annual Reports in Medicinal Chemistry 17, 301 (1982).
73. O.J. McConnell, R.E. Longley and F.E. Koehn, in: V.P. Gullo (ed.): The Discovery of Natural Products with Therapeutic Potential, Butterworth-Heinemann, Boston 1994, p. 109.
74. A.J. Weinheimer and R.L. Spraggins: Tetrahedron Lett. 10, 5285 (1969).
75. P.N. Kaul and C.J. Sindermann (eds.): Drugs and Food From the Sea-myth or reality, Oklahoma Univ. Press, Norman 1978.
76. P.N. Kaul: Fed. Proc. 40, 10 (1981).
77. P.J. Scheuer (ed.): Marine Natural Products; Chemical and Biological Perspectives, vol. I and II, Academic Press, New York 1978.
78. G.R. Pettit, C.L. Herald, D.L. Doubej and D.L. Herald: J. Am. Chem. Soc. 104, 6846 (1982).
79. D.J. Newman: Natural Products Division, National Cancer Institute, N.I.H., USA, fax mail communication, July 1997.
80. G.S. Bigaami, F. Wagner, P.G. Grothaus, P. Rustogi, D.E. Davis and A.S. Kraft: Biochim-Biophys-Acta 1312, 197 (1996).
81. X. Zhang, R. Zhang, H. Zhao, H. Cai, K.A. Gush, R.G. Kerr, G.R. Pettit and A.S. Kraft: Cancer Res. 56, 802 (1996).
82. A.S. Kraft, S. Woodley, G.R. Pettit, F. Gao, J.C. Coll and F. Wagner: Cancer-Chemother-Pharmacol. 37, 271 (1996).
83. K.L. Rinehart, V. Kishore, K.C. Bible, R. Saki, D.W. Sullivan and K.M. Li: J. Nat. Prod. 51, 1 (1988).
84. G.R. Pettit, Y. Kamano, C.L. Herald, C.A.A. Tuinman, F.E. Boettner, H. Kizu, J.M. Schmidt, L. Baczynskyj, K.B. Tomer and R.J. Bontems: J. Am. Chem. Soc. 109, 6883 (1987).
85. T.R. Norton, S. Shibata, M. Kashigawa and J. Bentley: J. Pharm. Sci. 65, 1368 (1976).
86. B.A. Gorshkov, V.A. Stonik and G.B. Elyakov: Toxicon 20, 655 (1982).
87. K. Tachibana, P.J. Scheuer, Y. Tsukitani, H. Kiruchi and D. van Engen: J. Am. Chem. Soc. 103, 2469 (1981).
88. M. Isobe, Y. Ichikawa and T. Goto: Tetrahedron Lett. 27, 963 (1986).
89. I. Spector, R.R. Schochet, Y. Kashman and A. Groweiss: Science 219, 493 (1983).
90. G. Lindgren, L. Bohlin and J. Bergman: Tetrahedron Lett. 27, 3283 (1986).
91. H. Nakashima, Y. Kido, N. Kobayashi, Y. Motoki, M. Neeshul and N. Yamamoto: J. Cancer Res. Clin. Oncol. 113, 413 (1987).
92. K.B. Glaser and R.J. Jacobs: Biochem. Pharmacol. 35, 449 (1986).
93. L.A. Wheeler, G. Sachs, G.W. deVries, D. Goodrum, E. Woldemus and S. Muallem: J. Biol. Chem. 262, 6531 (1987).
94. S. Hall and G. Strichartz (eds.): Marine Toxins - Origin, Structure and Molecular Pharmacology, Am. Chem. Soc., Washington DC 1990.
95. K. Nakanishi: Toxicon 23, 473 (1985).
96. P.N. Kaul, M.R. Farmer and I.S. Ciereszko: Proc. West. Pharmacol. Soc. 17, 294 (1974).
97. P.N. Kaul, in: H.H. Weber and G. Ruggieri (eds.): Food and Drugs from the Sea, Proc., Marine Technol Soc., Washington DC 1976, p. 311.
98. G. Strichartz: in ref. [89], p. 202.
99. J. Redondo, B. Fiedler and G. Scheiner-Bobis: Molecular Pharmacology 49, 49 (1996).
100. J.T. Baker, R.P. Borris, B. Carte, G.A. Cordell, D.D. Soejarto, G.M. Cragg, M.P. Gupta, M.M. Iwu, D.R. Madulid and V.E. Tyler: J. Nat. Prod. 58, 1325 (1995).
101. C.A. Ramsden (ed.): Quantitative Drug Design, vol. IV of the Comprehensive Medicinal Chemistry Series, Pergamon Press, Oxford 1990.
102. C.R. Bedell: The Design of Drugs to Macromolecular Targets, Wiley, New York 1992.
103. I.D. Kunz: Science 257, 1078 (1992).
104. M.A. Navia and D.A. Peattle: Trends Pharmacol. Sci. 14, 189 (1993).
105. G.R. Marshall, in: M.E. Wolff (ed.): Burger's Medicinal Chemistry and Drug Discovery, 5th edit., Wiley, New York 1995, pp. 573-659.
106. J.G. Henkel and E.M. Billings, in: W.O. Foye, T.L. Lemke and D.A. Williams (eds.): Medicinal Chemistry, 5th edit., Williams & Wilkins, New York 1995, pp. 58-74.
107. T.J. Marrone, J.M. Briggs and J.A. McCammon: Annu. Rev. Pharmacol. Toxicol. 37, 71 (1997).
108. C.H. Reynolds, M.K. Holloway and H.K. Cox (eds.): Computer Aided Molecular Design, Am. Chem. Soc., Washington, D.C. 1995.
109. A. Crum-Brown and T.R. Frazer: Trans. Roy. Soc. Edinburgh 25, 151 (1868).
110. R.L. Lipnick: Trends Pharmacol. Sci. 10, 265 (1989).
111. J.F. Danielli: J. Physiol. 100, 117 (1941).
112. H. Davson and J.F. Danielli: The Permeability of Natural Membranes, Cambridge Univ. Press 1952.
113. C. Hansch and T. Fujita: J. Amer. Chem. Soc. 86, 1616 (1964).
114. S.M. Free Jr. and J.W. Wilson: J. Med. Chem. 7, 395 (1964).
115. H. van de Waterbeemd and B. Testa: Adv. Drug Res. 16, 85 (1987).
116. H. van de Waterbeemd, P. Carrupt and N.E. Tayar, in: J.L. Fanchere (ed.): QSAR: Quantitative Structure-Activity Relationships in Drug Design, Prog. Clin. Biol. Res. 291, 101 (1989).
117. D.B. Boyd and C.M. Seward, in: C. Silipo and A. Vittoria (eds.): QSAR: Rational Approaches to the Design of Bioactive Compounds, Pharmacochem. Libr. Vol. 16, Elsevier, New York 1991, p. 167.
118. H. Kubinyi, in: M.E. Wolff (ed.): Burger's Medicinal Chemistry and Drug Discovery, 5th edit., Williams & Wilkins, New York 1995, p. 167.
119. R.D. Heilman: Qual. Assur. 4 (1), 75 (1995).
120. Quanta/Insight II/Cerius 2: Molecular Simulations Inc., 9685 Scranton Road, San Diego, CA 92121, USA.
121. Sybyl: Tripos, Inc., 1699 South Hanley Road, St. Louis, MO 63144, USA.
122. CAChe: CAChe Scientific, Inc., P.O. Box 4003, Beaverton, OR 97076, USA.
123. MacroModel: Chemistry Department, Columbia Univ., New York, NY 10032, USA.
124. Grasp: Department of Biochemistry and Molecular Biophysics, Columbia Univ., New York, NY 10032, USA.
125. D.J. Filman, J.T. Bolin, D.A. Mathews and J. Kraut: J. Biol. Chem. 257, 13663 (1982).
126. T. Clark: A Handbook of Computational Chemistry, Wiley-Interscience, New York 1985.
127. S.J. Wodak and J. Janin: J. Mol. Biol. 124, 323 (1978).
128. T.N. Hart and R.J. Read: Proteins; Struct. Funct. Genet. 13, 206 (1992).
129. J.D. Guntz, J.M. Blaney, S.J. Oatley, R. Langridge and I.E. Ferrin: J. Mol. Biol. 161, 269 (1982).
130. R.S. Judson, E.P. Jaeger and A.M. Treasurywala: J. Mol. Struct. Theochem. 308, 191 (1994).
131. G. Jones, P. Willett and R.C. Geln: J. Mol. Biol. 245, 43 (1995).
132. K.P. Clark and Y. Aja: J. Comput. Chem. 16, 1210 (1995).
133. K. Golukota, S. Vajda and C. DeLisi: J. Comput. Chem. 17, 418 (1996).
134. M. Miller, M. Jaskolski, J.K.M. Rao, J. Leis and A. Wlodawer: Nature 337, 576 (1989).
135. M. Miller, B.K. Sathyanarayana, A. Wlodawer, M.B. Toth, G.R. Marshall, L. Clawson, L. Selk, J. Schneider and S.B.H. Kent: Science 246, 1149 (1989).
136. C.M.W. Ho and G.R. Marshall: J. Comput. Aided Mol. Des. 4, 337 (1990).
137. R. Rosenfeld, S. Vajda and C. DeLisi: Annu. Rev. Biophys. Biomol. Struct. 24, 677 (1995).
138. T.P. Lybrand: Curr. Opin. Struct. Biol. 5, 224 (1995).
139. G. Jones and P. Willett: Curr. Opin. Biotechnol. 6, 652 (1995).
140. B.K. Schoichet and I. Kuntz: Chem. & Biol. 3, 151 (1996).
141. D.H. Allen, J.E. Davies, J.J. Galloy, O. Johnson, O. Kennard, C.F. Marcrea, E.M. Mitchell, G.F. Mitchell, J.M. Smith and D.G. Walson: J. Chem. Inf. Comput. Sci. 31, 187 (1991).
142. E.E. Abola, F.C. Bernstein and T.F. Koetzle, in: P.C. Glaeser (ed.): The Role of Data in Scientific Progress, Elsevier, New York 1985.
143. R.S. Pearlman: CONCORD User's Manual, Tripos Associates, Inc., St. Louis, MO, USA 1992.
144. R.S. Pearlman: Chem. Des. Auto. News 8, 3 (1993).
145. R.S. Pearlman and H. Kubinyi (eds.): 3-D QSAR in Drug Design; Theory, Methods and Applications, ESCOM Scientific, Leiden 1993, pp. 41-19.
146. R.P. Sheridan, A. Rusinko, R. Nilakantan and R. Venkataraghavan: Proc. Natl. Acad. Sci. (USA) 86, 8165 (1989).
147. P.R. Andrews, E.J. Lloyd, J.L. Martin and S.L.A. Munroe: J. Med. Graphics 4, 41 (1986).
148. P. Gund: Progr. Mol. Subcell. Biol. 11, 117 (1977).
149. A.M. Lesk: Commun, of the A.C.M. 22, 219 (1979).
150. S.E. Jakes and P. Willett: J. Mol. Graphics 4, 12 (1986).
151. S.E. Jakes, N. Watts, P. Willett, D. Bawden and J.D. Fisher: J. Mol. Graphics 5, 41 (1987).
152. P.A. Bartlett, G.T. Shea, S.J. Telfer and S. Waterman, in: S.M. Roberts (ed.): Molecular Recognition: Chemical and Biological Problems, Royal Society of Chemistry, London 1989, pp. 182-186.
153. J.H. van Drie, D. Weininger and Y.C. Martin: J. Comput. Aided Mol. Des. 3, 225 (1989).
154. R.P. Sheridan, R. Nilakantan, A.I. Rusinko, N. Bauman, K.S. Haraki and R. Venkataraghavan: J. Chem. Inf. Comput. Sci. 29, 225 (1989).
155. Tripos Associates, Inc., St Louis, MO, USA 1992.
156. A. Catfish, A. Miranker and M. Karplus: J. Med. Chem. 36, 2142 (1993).
157. M.B. Eisen, D.C. Wiley, M. Karplus and R.E. Hubbard: Proteins: Strut. Funct. Genet. 19, 199 (1994).
158. H.J. Bohm: J. Comput. Aided Mol. Des. 6, 61 (1992).
159. G. Lauri and P.A. Bartlett: J. Comput. Aided Mol. Des. 8, 51 (1994).
160. D.K. Gehlhaar, K.E. Moerder, D. Zichi, C.J. Sherman, R.C. Ogden and S.T. Freer: J. Med. Chem. 38, 466 (1995).
161. M. Laguerre, J.-P. Dubost, E. Kummer and A. Carpy: Drug Des. Discov. 11, 205 (1994).
162. E. Audry, J.P. Dubost, J.C. Colleter and Ph. Dallet: Eur. J. Mol. Chem. 21, 71 (1986).
163. G.L. Olson (ed.): Proceedings of the Symposium on Structure and Drug Design, Drug Des. Discov. 13, 1-168 (1995).
164. J.R. Knox and P.C. Moews: J. Mol. Biol. 220, 435 (1991).
165. G. Givaraghi: Eur. J. Med. Chem.(Suppl.) 30, 467s (1995).
166. M.F. Hilbert, S. Trumpp-Kallmeyer, A. Bruinwells and J. Hoflack: Mol. Pharmacol. 40, 8 (1991).
167. G. Nordvall and U. Hacksell: J. Med. Chem. 36, 967 (1993).
168. T.L. Blundell, B.L. Sibanda, M.J.E. Sternberg and J.M. Thornton: Nature 326, 347 (1987).
169. L.H. Pearl and W.R. Taylor: Nature 329, 351 (1987).
170. M.A. Gallop, R.W. Barrett, W.J. Dower, S.P.A. Fodor and E.M. Gordon: J. Med. Chem. 37, 1233 (1994).
171. E.M. Gordon, R.W. Barrett, W.J. Dower, S.P.A. Fodor and M.A. Gallop: J. Med. Chem. 37, 1385 (1994).
172. E.R. Feldor: Chimia 48, 531 (1994).
173. K.D. Janda: Proc. Soc. Natl. Acad. Sci. USA 91, 10779 (1994).
174. R.M. Baum: Chem. Eng. News 72 (6), 20 (1994).
175. D. Madden, V. Krehnak and M. Lebl: Perspct. Drug Discov. Des. 2, 269 (1994).
176. J. Rohr: Angew. Chem. Int. Ed. Engl. 34, 881 (1995).
177. L.A. Thompson and J.A. Ellman: Chem. Rev. 96, 555 (1996).
178. A.A. Patchett: J. Med. Chem. 36, 2051 (1993).
179. S.L. Danheiser: Genetic Eng. News 13 (Nov. 15), 1 (1993).
180. P.M. Sweetnam, C.H. Price and J.W. Ferkany, in: M.E. Wolff (ed.): Burger's Medicinal Chemistry and Drug Discovery, Wiley-Interscience, New York 1995, 5th edit., pp. 697-731.
181. R.B. Merrifield: J. Am. Chem. Soc. 85, 2149 (1963).
182. C.C. Leznoff: Acct. Chem. Res. 11, 327 (1978).
183. J.M.J. Frechet: Tetrahedron 37, 663 (1981).
184. P. Hodge and D.C. Sherrington (eds.): Polymer Supported Reactions in Organic Synthesis, Wiley-Interscience, Chichester 1980.
185. B.A. Bunin and J.A. Ellman: J. Am. Chem. Soc. 114, 10997 (1992).
186. S.H. Dewitt, J.S. Kiely, C.J. Stankovic, M.C. Schroeder, D.M.R. Cody and M.R. Pavia: Proc. Natl. Acad. Sci., USA 90, 6909 [1993].
187. J.S. Fruchtel and G. Jung: Angew. Chem. Int. Ed. Eng. 35, 17 (1996).
188. S.R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Synthesis and Applications, Wiley, New York 1997.
189. B.A. Bunin, M.J. Plunkett and J.A. Ellman: New J. Chem. 21, 125 (1997).
190. G.G. Look, C.P. Holmes, J.P. Chinn and M.A. Gallop: J. Org. Chem. 59, 7588 (1994).
191. A. Borchardt and W.C. Still: J. Am. Chem. Soc. 116, 373 (1994).
192. W.C. Still: Acc. Chem. Res. 29, 155 (1996).
193. S.P.A. Fodor, J.L. Read, M.C. Pirrung, L. Stryer, A.T. Lu and D. Solas: Science 251, 767 (1991).
194. C.P. Holmes, C.L. Adams, L.M. Kochersperger, R.B. Mortensen and L.A. Aldwin: Biopolymers 37, 199 (1995).
195. R. Frank: Tetrahedron 42, 9217 (1992).
196. K.C. Nicolaou, X.-Y. Xiao, Z. Parandoosh, A. Senyei and M.P. Nova: Angew. Chem. Int. Ed. Engl. 34, 2289 (1995).
197. X.-Y. Xiao and M.P. Nova, in: R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Wiley, New York 1997, pp. 135-152, 1997.
198. T. Carell, E.A. Wintner, A. Bashir-Hashemi and J. Rebek Jr.: Angew. Chem. Int. Ed. Eng. 33, 2005 (1994).
199. D.P. Curan: Chemtracts 9, 75 (1996).
200. R.W. Armstrong, S.D. Brown, T.A. Keating and P.A. Tempest, in: S.R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Wiley, New York 1997, pp. 153-190.
201. R.N. Zuckerman, J.M. Kerr, M.A. Siani and S.C. Banvile: Int. J. Peptide Protein Res. 40, 497 (1992).
202. V. Glaser: Genetic Eng. 16, 1 (1996).
203. M. Kapis (ed.): Non-Animal Techniques in Biomedical and Behavioral Research and Testing. Lavis Publishers, Boca Raton Fl. 1993.
204. J.R. Broach and J. Thorner: Nature 384, 14 (1996).
205. S.P.A. Fodor, R.P. Rava, C. Huang, A.C. Pease, C.P. Holmes and C.L. Adams: Nature, 364, 555 (1993).
206. M.H.J. Ohlmeyer, R.N. Swanson, L.W. Dillard, J.C. Reader, G. Asouline, R. Kobayashi, M. Wigler and W.C. Still: Proc. Natl. Acad. Sci. USA 90, 10922 (1993).
207. J.S. McLean: Trends Biotechnol. 11, 232 (1993).
208. P. Bevan, H. Ryder and I. Shaw: Trends Biotechnol. 13, 115 (1995).
209. W.H.M.L. Luyten and J.E. Leysen: Trends Biotechnol. 11, 247 (1993).
210. R. Anand: Trends Biotechnol. 15, 42 (1997).
211. J.M. Kerr, S.C. Banville and R.N. Zuckerman: J. Am. Chem. Soc. 115, 2529 (1993).
212. P.G. Stockley: Trends Biotechnol. 14, 39 (1996).
213. G.W.A. Milne, S. Wang and M.C. Nicklaus: J. Chem. Inf. Comput. Sci. 36, 726 (1996).
214. S. Schulze-Kremer (ed.): Advances in Molecular Bioinformatics. IOS Press, Washington, DC 1994.
215. D. Schomburg and U. Lessel (eds.): Bioinformatics: From Nucleic Acids and Proteins to Cell Metabolism. GBF Monograph 18 (1995).
216. M.J.E. Sternberg, J.D. Hirst, R.A. Lewis, R.D. King, A. Srinivasan and S. Muggleton: in ref. [207], pp. 1-8.
217. H. Bauknecht, A. Zell, H. Bayer, P. Levi, M. Wagener, J. Sadowski and J. Gasteiger: in ref. [208], pp. 153-167.
218. H.-G. Lipinski: in ref. [208], pp. 185-195.
219. P.N. Judson, J. Fox and P.J. Krause: J. Chem. Comput. Sci. 36, 621 (1996).
220. A.E. Madvedev, A.S. Ivanov, A.V. Veselovsky, V.S. Skvortsov and A.I. Archakov: J. Chem. Inf. Comput. Sci. 36, 664 (1996).
221. W. Karcher and S. Karabunarliev: J. Chem. Inf. Comput. Sci. 36, 672 (1996).
222. M. Grigarov, J. Weber, J.M.J. Tronchet, C.W. Jefford, W.K. Milhous and D. Marie: J.Chem. Inf. Comput. Sci. 37, 124 (1997).
223. K. Hasegawa, Y. Miyashita and K. Funatsu: J. Chem. Inf. Comput. Sci. 37, 306 (1997).
224. E. Estrada: J. Chem. Inf. Comput. Sci. 37, 320 (1997).
225. N.E. Schmetulskis, D. Weininger, C.J. Blankley, J.J. Yang and C. Humblet: J. Chem. Inf. Comput. Sci. 36, 862 (1996).
226. M.S. Molchanova, V.V. Shcherbukhin and N.S. Zefritov: J. Chem. Inf. Comput. Sci. 36, 888 (1996).
227. D.A. Thorner, D.J. Wild, P. Willett and P.M. Wright: J. Chem. Inf. Comput. Sci. 36, 900 (1996).
228. S. Ash, M.A. Cline, R.W. Homer, T. Hurst and G.B. Smith: J. Chem. Inf. Comput. Sci. 37, 71 (1997).
229. J. Palanski: J. Chem. Inf. Comput. Sci. 37, 553 (1997).
230. R.A. Lewis, J.S. Mason and L.M. McLay: J. Chem. Inf. Sci. 37, 599 (1997).
231. C.J. Armstrong (ed.): World Databases in Chemistry, World Databases Series, Bowker Saur, New Jersey 1996.
232. http://vrml.wired.com/vrml.tech/vrml.10-3.html
233. Brickmann and H. Vollhardt: Trends Biotechnol. 14, 167 (1996).
234. W. Bains: Trends Biotechnol. 14, 37 (1996).
235. Trends in Biotechnology 14 (8), 261 (1996).
236. Courtesy of Pangea Systems Inc., 1301 Marina Village Parkway, California 94501, USA.
237. J.N. Langley: J. Physiol. 33, 374 (1905).
238. P. Ehrlich, in: F. Himmelweit (ed.): Collected Pages of Paul Ehrlich, vol. III., Pergamon, London 1957.
239. R.M. Evans: Science 240, 884 (1988).
240. B.K. Kobilka: Annu. Rev. Neurosci. 15, 87 (1992).
241. A.G. Gilman: Annu. Rev. Neurosci. 56, 615 (1987).
242. A. Brisson and P.N.T. Unwin: Nature 315, 474 (1985).
243. J.A. Kemp and P.D. Leeson: Trends Pharmacol. Sci. 14, 20 (1993).
244. R.P. Ahlquist: Am. J. Physiol. 153, 586 (1948).
245. J.W. Black, W.A.M. Duncan, G.J. Durant, C.R. Ganellin and M.E. Parsons: Nature 236, 385 (1972).
246. A.M. Creighton and S. Turner (eds.): The Chemical Regulation of Biological Mechanisms, Royal Society of Chemistry, London 1982.
247. K.P. Minneman and T.A. Esbenshade: Annu. Rev. Pharmacol. Toxicol. 34, 117 (1994).
248. A. Wlodawer and J.W. Erickson: Annu. Rev. Biochem. 62, 543 (1993).
249. K. Appelt: Perspect. Drug Discovery Des. 1, 23 (1993).
250. T. Clackson and J.A. Wells: Science 267, 383 (1995).
251. S. Miyamoto and P.A. Kollman: Proc. Natl. Acad. Sci. USA 90, 8402 (1993).
252. P.A. Rejto and G.M. Verkhivker: Proc. Natl. Acad. Sci. USA 93, 8945 (1996).
253. M. Williams: Med. Res. Rev. 11, 147 (1991).
254. H.A. Lester: Science 241, 1057 (1988).
255. P. Sokoloff, M.P. Martres, B. Giros, M.-L. Bouthenet and J.-C. Schwartz: Biochem. Pharmacol. 43, 659 (1992).
256. T. Kenakin: Molecular Pharmacology, Blackwell Science, Cambridge 1997, pp. 64-91.
257. O. Civelli, J.R. Bunzow, D.K. Grandy, Q.-Y. Zhou and H.H.M. van Tol: Eur. J. Pharmacol. 207, 277 (1991).
258. C. Wahlestedt, E.M. Pich, G.F. Koob, F. Yee and M. Heilig: Science 259, 528 (1993).
259. C.D. Strader, T. Gaffney, E.E. Sugg, M.R. Candelore, R. Keys, A.A. Patchett and R.A.F. Dixon: J. Biol. Chem. 266, 5 (1991).
260. W.L. Duax and J.F. Griffin: Adv. Drug Res. 18, 115 (1989).
261. G. Burnstock, in: R.W. Straub and L. Bolis (eds.): Cell Membrane Receptors for Drugs and Hormones; A Multidisciplinary Approach, Raven Press, New York 1978, pp. 107-18.
262. T.K. Harden, J.L. Boyer and R.A. Nicholas: Annu. Rev. Pharmacol. Taxicol. 35, 541 (1995).
263. J.R. Helper and A.G. Gilman: Trends Biochem. Sci. 17, 383 (1992).
264. W. Siess: Physiol. Rev. 69, 58 (1989).
265. S.M. Hourani and N.J. Cusack: Pharmacol. Rev. 43, 243 (1991).
266. C.E. Parr, D.M. Sullivan, A.M. Paradiso, E.R. Lazarowski, L.H. Burch, J.C. Olsen, L.H. Erb, G.A. Weisman, R.C. Boucher and J.T. Turner: Proc. Natl. Acad. Sci. USA 91, 3275 (1994).
267. H. Ren and G.L. Stiles: J. Biol. Chem. 269, 3104 (1994).
268. T.J. Furlong, K.D. Pierce, L.A. Selbie and J. Shine: Mol. Brain Res. 15, 62 (1992).
269. K.D. Pierce, T.J. Furlong, L.A. Selbie and J. Shine: Biochem. Biophys. Res. Commun. 187, 86 (1992).
270. C.A. Salvatore, M.A. Jacobson, H.E. Taylor, J. Linden and R.G. Johnson: Proc. Natl. Acad. Sci. USA 546, 69 (1991).
271. M.E. Olah and G.L. Stiles: Annu. Res. Pharmacol. Toxicol. 35, 581 (1995).
272. J.M. Downey, G.S. Liu and J.D. Thornton: Cardiovasc. Res. 27, 3 (1993).
273. K.K. Griendling, B. Lassegue and W. Alexander: Annu. Rev. Pharmacol. Toxicol. 36, 281 (1995).
274. M. de Gasparo, A. Hussain, W. Alexander, K.J. Catt, A.T. Chiu, M. Drew, T. Goodfriend, J.W. Harding, T. Inagami and P.B. Timmermans: Hypertension 25, 924 (1995).
275. H. Furuta, D.F. Guo and T. Inagami: Biochem. Biophys. Res. Commun. 183, 8 (1992).
276. M. Mukoyama, M. Nakajima, M. Horiuchi, H. Sasamura, R.E. Pratt and V.J. Dzau: J. Biol. Chem. 268, 24539 (1993).
277. M. Ito, M.I. Oliverio, P.J. Mannon, C.F. Best, N. Maeda, O. Smithies and T.M. Coffman: Proc. Soc. Natl. Acad. Sci. USA 92, 3521 (1995).
278. A.H. Gradman, K.E. Arcuri, A.I. Goldberg, L.S. Ikeda, E.B. Nelson, D.B. Snavely and C.S. Sweet: Hypertension 25, 1345 (1995).
279. A.D. Strosberg: Annu. Rev. Pharmacol. Toxicol. 37, 421 (1997).
280. A.D. Strosberg: Protein Sci. 12, 1198 (1993).
281. D.S. Hartman and O. Civelli: Ann. Med. 28, 211 (1996).
282. J.P. Moore and R.W. Sweet: Perspect. Drug Discovery Des. 1, 235 (1993).
283. G.A.M. Giardina, H.M. Sarau, C. Farina, A.D. Medhurst, M. Grugni, L.F. Riveglia, D.B. Schmidt, R. Rigolio, M. Luttmann, V. Vecchietti and D.W.P. Hay: J. Med. Chem. 40, 1794 (1997).
284. A. Burgen and E.A. Barnard (eds.): Receptor Subunits and Complexes, Cambridge University Press 1992.
285. T.J. Maher, in: W.O. Foye, T.L. Lemke and D.A. Williams (eds.): Medicinal Chemistry, Williams & Watkins, Baltimore 1995, pp. 75-82.
286. K.S. Brown: The Scientist 11 (14), 1 (1997).
287. K.S. Brown: The Scientist 11 (6), 1 (1997).
288. Various groups of authors: J. Med. Chem. 40, 1112, 1201, 1422, 1820, 1876, 1901, 1906, 2113, 2156 (1997).
289. A. Muscate and G.L. Kenyon, in: M.E. Wolff (ed.): Burger's Medicinal Chemistry and Drug Discovery., Wiley-Interscience, New York 1995, p. 734.
290. B.R. Baker: Design of Active Site-Directed Irreversible Enzyme Inhibitors, Wiley, New York 1967.
291. R.R. Rando: Pharmacol. Rev. 36, 111 (1984).
292. P. Furman, M. St. Claire and T. Spector: J. Biol. Chem. 259, 9575 (1989).
293. R. Labia, V. Lelievre and J. Peduzzi: Biochim. Biophys. Acta. 611, 351 (1980).
294. D.G. Brenner and J.R. Knowles: Biochem. 23, 5833 (1984).
295. J.A. Sabine: Cholesterol, Marcel Dekker, New York 1977.
296. A. Alberts: Proc. Natl. Acad. Sci. 77, 3957 (1980).
297. G.R. Stark and P.A. Bartlett: Pharmac. Ther. 23, 45 (1983).
298. P. Nuhn and T. Koehler: Pharmazie 46, 365 (1991).
299. R.H. Abeles and T.A. Alston: J. Biol. Chem. 265, 16705 (1990).
300. pp. 737-779 in ref. [277].
301. R.B. Silverman: Mechanism-Based Enzyme Inactivators, Chemistry and Enzymology, CRC Press, Boca Raton 1988.
302. R.H. Abeles: Pure & Applied Chemistry 53, 149 (1980).
303. R.H. Kalman: Drug Dev. Res. 1, 311 (1981).
304. C.T. Walsh: Annu. Rev. Biochem. 53, 493 (1984).
305. Y. Nishizuka: Science 258, 607 (1992).
306. J.H. Exton: J. Biol. Chem. 265, 1 (1990).
307. Y. Asaoka, M. Oka, Y. Yoshida and Y. Nishizuka: Proc. Natl. Acad. Sci. USA 88, 8681 (1991).
308. N. Berry and Y. Nishizuka: Eur. J. Biochem. 189, 205 (1990).
309. F. William, F. Wagner, M. Karin and A.S. Kraft: J. Biol. Chem. 265, 18166 (1990).
310. Y. Nishizuka: Nature 282, 815 (1992).
311. L.M. Schwartz and C.E. Milligan: Trends Neurosci. 19, 535 (1996).
312. R.E. Dolle, C.V.C. Prasad, C.P. Prouty, J.M. Salvino, M.M.A. Awad, S.J. Schmidt, D. Hoyer, T.M. Ross, T.L. Graybill, G.J. Speier, J. Uhl, B.E. Miller, C.T. Helaszek and M.A. Ator: J. Med. Chem. 40, 1941 (1997).
313. S. Niwata, H. Fukami, M. Sumida, A. Ito, S. Kakutani, M. Saitoh, K. Suzuki, Imoto, H. Shibata, S. Imajo, Y. Kiso, T. Tanaka et al.: J. Med. Chem. 40, 2156 (1997).
314. R.R. Bernstein: Perspec. Biol. Med. 33, 4 (1990).
315. S.P. Buchbinder, M.H. Katz, N.A. Hessol, P.M. O'Malley and S.D. Holmberg: AIDS 8 (8), 1123 (1994).
316. P.S. Sarin and A.L. Goldstein: Immunopharmacol. Immunotoxicol. 17, 217 (1995).
317. N.E. Khol, E.A. Emini, W.A. Schlief, L.J. Davis, J.C. Heimbach, R.A.F. Dixon, E.M. Scolnick and I.S. Sigal: Proc. Natl. Acad. Sci. USA 85, 4686 (1988).
318. P.L. Beaulieu, D. Wernic, A. Abraham, P.C. Anderson, T. Bogri, Y. Bousquet, G. Croteau, I. Guse, D. Lamarre, F. Liard, W. Paris, D. Thibeault, S. Pav and L. Thong: J. Med. Chem. 40, 2164 (1997).
319. J.L. Dinerman, T.M. Dawson and M.J. Shell: Proc. Natl. Acad. Sci. USA 91, 4214 (1994).
320. J. Garthwaite, S.L. Charles and R. Chess-Williams: Nature 336, 385 (1988).
321. D.S. Bredt and S.H. Snyder: Proc. Natl. Acad. Sci. USA 87, 682 (1990).
322. M.A. Marletta: J. Biol. Chem. 268, 12231 (1993).
323. D.S. Bredt and S.H. Snyder: Annu. Rev. Biochem. 63, 175 (1994).
324. T.M. Dawson and V.L. Dawson: Annu. Rev. Med. 47, 219 (1996).
325. M.A. Marletta: J. Med. Chem. 37, 1899 (1994).
326. J.E. Ogden and P.K. Moore: Trends Biotechnol. 13, 70 (1995).
327. J. Pfeilschifter, W. Eberhardt, R. Hummel, D. Kuntz, H. Muehl, D. Nitsch, C. Pluess and G. Walker: Cell Biol. Int. 20, 51 (1996).
328. J.-J. Toulme and C. Helene: Gene 72, 51 (1988).
329. M.L. Stephenson and P.C. Zamecnik: Proc. Natl. Acad. Sci. USA 75, 285 (1978).
330. E. Uhlmann and A. Peyman: Chem. Rev. 90, 543 (1990).
331. R.J. Jones, K.-Y. Lin, J.F. Milligan, S. Wadwani and M.D. Matteucci: J. Org. Chem. 58, 2983 (1993).
332. A. de Mesmaeker, A. Waldner, V. Fritsch and R.M. Wolf: Eur. J. Med. Chem. (Suppl.) 30, 479s (1995).
333. A.R. Heider and T.J. Bardos, in: W.O. Foye (ed.): Cancer Chemotherapeutic Agents, Am. Chem. Soc., Washington, DC 1995, pp. 529-576.
334. A. Helene and J.-J. Toulme: Biochim. Biophys. Acta. 1049, 99 (1990).
335. C.A. Stein and Y.-C. Cheng: Science 261, 1004 (1993).
336. S.T. Crooke and C.F. Bennett: Annu. Rev. Pharmacol. Toxicol. 36, 107 (1996).
337. C.A. Stein and A.M. Krieg: Antisense Res. Dev. 4, 67 (1994).
338. J.-S. Sun and C. Helene: Curr. Opin. Struct. Biol. 3, 345 (1993).
339. L.J. Maher III, B. Wold and P.B. Dervan: Science 245, 725 (1989).
340. G. Felsenfeld, D.R. Davies and A. Rich: J. Am. Chem. Soc. 79, 2023 (1957).
341. W.I. Sundquist and A. Klug: Nature 342, 825 (1989).
342. M. Salunkhe, T. Wu and R.L. Letsinger: J. Annu. Chem. Soc. 114, 8768 (1992).
343. E.T. Kool: J. Ann. Chem. Soc. 113, 6265 (1991).
344. E.T. Kool: Annu. Rev. Biophys. Biomol. Struct. 25, 1 (1996).
345. S. Agrawal: Trends Biotechnol 14, 121 (1996).
346. S.T. Crooke, in: J.T. August (ed.): Gene Therapy, Advances in Pharmacology 40, 1 (1997).
347. S. Jeffcoate: Trends Biotechnol. 14, 121 (1996).
348. G.A. Evans: Trends Biotechnol. 14, 143 (1996).
349. World Wide Web address: http://nt.excite.com/ntd.gw, news May 7, 1997.
350. L.J. Beeley and D.M. Duckworth: Drug Discovery Today 1, 474 (1996).
351. T.J.R. Harris: Genet. Eng. 4, 127 (1983).
352. T.J.R. Harris, in: C.R. Ganellin and S.M. Roberts (eds.): Medicinal Chemistry, Academic Press, London 1993, pp. 103-120.
353. L.M. Fisher: New York Times, July 26 (1997).
354. Eastern Pharmacist: 40 (472), 101 (1997).
355. S.-Y. Chang and S. Chang, in: Y. Okami, T. Beppu and H. Ogawara (eds.): Biology of Actinomycetes, '88-Proceedings of the Seventh International Symposium on Biology of Actinomycetes, Japan Scientific Society Press, Tokyo 1988, pp. 103-107.
356. L.T. Malek, in: P.A. Barnacal (ed.): Pharmaceutical Biotechnology International, Sterling Publications, London 1995, pp.55-57.
357. M. Gilbert, R. Morosoli, F. Shareck and D. Kluefel: Crit. Rev. Biotechnol. 15, 13 (1995).
358. C. Binnie, J.D. Cossar and D.I.H. Stewart: Trends Biotechnol. 75, 315 (1997).
359. M.P. Murphy: Trends Biotechnol. 15, 326 (1997).
360. K. Koya, Y. Li, H. Wang, T. Ukai, N. Tatsuta, M. Kawakami, Shishido and L.B. Chen: Cancer Res. 56, 538 (1996).
361. X. Sun, J.R. Wong, K. Song, J. Hu, K.D. Garlid and L.B. Chen: Cancer Res. 54, 1465 (1994).
362. W.A. Haseltine: Scientific American 276 (3), p. 92, (1992).
363. Human Genome Project Information: http:www.ornl.gov/hgmis/timeline.html
364. Eastern Pharmacist: 40 (372), 105 (1997).
365. R.M. Blaese: Scientific American 276 (6), 111 (1997).
366. T. Friedman: Scientific American 276 (6), 95 (1997).
367. P.L. Felgner: Scientific American 276 (6), 102 (1997).
368. G. Parmiani, M.P. Colombo, C. Melani and F. Arienti, in: J.T. August (ed.): Gene Therapy. Advances in Pharmacology 40, 259 (1997).
369. W.E. Paul and R.A. Seder: Cell (Cambridge, Mass.) 76, 241 (1994).
370. E. Robey and J.P. Allison: Immunol. Today 16, 306 (1995).
371. D.L. Shawler, H. Fakhrai, C.V. Beveren, D. Mercola, D.P. Gold, R.M. Barthomolomew, I. Royston and R.E. Sobol, in: J.T. August (ed.): Gene Therapy, Advances in Pharmacology 40, 309 (1997).
372. R.E. Sobol, H. Fakhrai, D.L. Shawler, R. Gjerset, O. Dorigo, C. Carson, T. Khaleghi, J. Koziol, T.A. Shiftan and I. Royston: Gene Therapy 2, 164 (1995).
373. J.H. White, in: J.T. August (ed.): Gene Therapy; Advances in Pharmacology 40, 339 (1997).
374. C.P. Hodson: Bio/Technology 13, 222 (1995).
375. S.B. Prusiner: Science 216, 136 (1982).
376. S.B. Prusiner: Science 252, 1515 (1991).
377. S.B. Prusiner: Eur. J. Med. Chem. (Suppl.) 30, 11s (1995).
378. H. Fraser and A.G. Dickinson: J. Comp. Pathol. 83, 29 (1973).
379. A. Taraboulos, K. Jendroska, D. Serban, S.-L. Yang, S.J. de Armond and S.B. Prusiner: Proc. Natl. Acad. Sci. USA 89, 7620 (1992).
380. S.J. de Armond, S.-L. Yang, A. Lee, R. Bowler, A. Taraboulos, D. Groth and S.B. Prusiner: Proc. Natl. Acad. Sci. USA 90, 6449 (1993).
381. S.W. Davies and G.P. Bates: Cell 90, 537 (1997).
382. D.T. Curiel, in: J.T. August (ed.): Gene Therapy, Advances in Pharmacology 40, 51 (1997).
383. W.H. Verlander, H. Lubon and W.N. Drohan: Scientific American 276 (1), 70 (1997).
384. K.Y. Kreeger: The Scientist 11 (15), 11 (1997).
385. S.W.F. Omta: Critical Success Factors in Biomedical Research and Pharmaceutical Innovation, Kluwer Academic Publications, Dordrecht 1995.
386. R. Liwis: The Scientist 11 (13), 1 (1997).
387. E.E. Codd, J.B. Press and R.B. Raffa: Life Sci. 56, 63 (1995).
388. 375a G.W. Bemis and M.A. Murcko: J. Med. Chem. 39, 2887 (1996).
389. Annual Report of the Pharmaceutical Research and Manufacturers of America (1996-1997)
390. H. von Doehren: e-mail 〈hans@cicsg.tk.tu-berlin.de〉
391. A.F. Horowitz: Scientific American 276 (5), 68 (1997).
392. M. Keller: Prevention 47 (5), 17 (1995).
393. J. McBride: Agricultural Res. 43 (1), 22 (1995).
394. P.L. DeVito: USA Today 123 (590), 27 (1994).
395. J. Licinio, P.W. Gold and M. Wong: Lancet 346, 104 (1995).
396. J.K. Klecolt-Glaser, P.T. Marucha, W.B. Malarky, A.M. Mercado and R. Glaser: Lancet 346, 1194 (1995).
397. Progress in Drug Research, Vol. 50 (E. Jucker, Ed.)