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Document Page 147 ultimately tested in a nontagged, solution-phase form. Perhaps more significant is that the success described here demonstrates a possible synergy between structure-based design and combinatorial methodology. This approach has many merits, but the most significant is the application of structurally directed libraries toward target binding-site structures which, for one reason or another, may not be fully characterized. This method serves to aim the combinatorial syntheses in a logical direction, rather than attempt to prepare libraries of vast diversify (and numbers). Finally, since the libraries of compounds that were prepared contained few members, it was possible to analytically characterize each of the pools to assess integrity of their composition. Overall, there are many important advantages in the paradigm we have adopted that make the strategy generally viable in the context of structure-based lead compound discovery. References 1. Greenbaum LM. Adv Exp Med Biol 1986; 198A:55. 2. Okamoto H, Greenbaum LM. Biochem Biophys Res Commun 1983; 112:701. 3. Muller-Esterl W. Thromb Haemost 1989; 61:2. 4. Bhoola KD, Figueroa CD, Worthy K. Pharmacol Rev 1992; 44:1. 5. Proud D, Perkins M, Pierce JV, Yates KN, Highet PF, Mangkornkanok/Mark M, Bahu R, Carone F, Pisano JJ. J Biol Chem 1981; 256:10634. 6. Kitamura N, Takagaki Y, Furoto S. Nature 1983; 305:545. 7. Ward PE. In: Burch RM, ed. Bradykinin Antagonists: Basic and Clinical Research. New York: Marcel Dekker, 1991:147–170. 8. Perkins MN, Campbell EA, Davis A, Dray A. Br J Pharmacol 1992; 107:237P. 9. Perkins MN, Campbell EA, Dray A. Pain 1993; 53:191. 10. Perkins MN, Kelly D. Br J Pharmacol 1993; 110:1441. 11. Kyle DJ, Burch RM. Curr Opin Invest Drugs 1993; 2:5. 12. Kyle DJ, Burch RM. Drugs of the Future 1992; 17(4):305. 13. Huang HM, Lin TA, Sun GY, Gibson GE. J Neurochem 1995; 64:761. 14. Rubin LE, Levi R. Circ Res 1995; 76:430. 15. Bao G, Gohlke P, Unger T. J Cardiovasc Pharmacol 1992; 20(Supplement 9):S96. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_147.html (1 of 2) [4/5/2004 5:00:59 PM]
Document 16. Martorana PA, Kettenbach B, Breipol G, Linz W, Scholkens BA. Eur J Pharmacol 1990; 182:395. 17. McDonald KM, Mock J, D' Ajoia M, Parrish T, Hauer K, Francis G, Stillman A, Cohn JN. Circulation 1995; 91(7):2043. 19. Kyle DJ, Blake PR, Hicks RP. In: Burch RM, ed. Bradykinin Antagonists: Basic and Clinical Research. New York: Marcel Dekker, 1991:131–146. 20. Chou PY, Fasman GD. Biophys J 1979; 26:367. 18. Schwieler JH, Kahan T, Nussberger J, Hjemdahl P. Am J Physiol 1993; 264:E631. 21. (a) Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathon S, Karplus MJ. CHARMM: a program for macromolecular energy minimization, and dynamics calculations. J Comp Chem 1983; 4:187–217. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_147.html (2 of 2) [4/5/2004 5:00:59 PM]
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Page 149 and 150: Document 4 Bradykinin Receptor Anta
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Document Table 1 Approval Indicatio
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Document Page 438 proteins. One pot
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Document Med Biol 1991; 306:9-21; (
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Document Page 629 ML, Clare M, Decr
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Document factors, 247 Combination t
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Document Cyclotheonamide A (CtA), 2
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Document D ddI, 152 tumour necrosis
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Document antistasin peptides, 281 c
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Document fragment-based programs, 5
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Document [Human immunodeficiency vi
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Document overview, 103-104, 108-109
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Document [Inhibitors] 2-((3,4-dihyd
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Document antagonistic activity, 416
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Document Kininogen, 119 high molecu
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Document RT inhibitor, 41, 56 Nonpe
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Document Phosphoglycerate kinase (P
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Document [Protease targets] serinyl
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