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Document 135. Mazzulli T, Rusconi S, Merrill DP, D'Auilla RT, Moonis M, Chou T-C, et al. Alternating verse continuous drug regimens in combination chemotherapy of human immunodeficiency virus type 1 infection in vitro. Antimicrob Agents Chemother 1994; 38:656–661. 136. Smith MS, Brian EL, De Clercq E, Pagano JS. Susceptibility of human immunodeficiency virus type 1 replication in vitro to acyclic adenosine analogs and synergy of the analogs with 3'-azido-3'deoxythymidine. Antimicrob Agents Chemother 1989; 33:1482–1486. 137. Dornsife RE, St. Clair MH, Huang AT, Panella TJ, Koszalka GW, Burns CL, et al. Anti-human immunodeficiency virus synergism by zidovudine (3'-azidothymi http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_79.html (2 of 2) [4/5/2004 4:53:21 PM]
Document dine) and didanosine (dideoxyinosine) contrasts with their additive inhibition of normal human marrow progenitor cells. Antimocrob Agents Chemother 1991; 35:322–328. 138. Antonelli G, Dianzani F, Bellarosa D, Turriziani O, Riva E, Gentile A. Drug combination of AZT and ddI: synergism of action and prevention of appearance of AZT-resistance. Antiviral Chem Chemother 1994; 5:51–55. 139. Balzarini J, Karlsson A, Perez-Perez MJ, Camarasa MJ, Tarpley WG, De Clercq E. Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy. J Virol 1993; 67:5353–5359. 140. Balzarini J, Perez-Perez M-J, Velazquez S, San-Felix A, Camarasa M-J, De Clercq E, et al. Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives). Proc Natl Acad Sci USA 1995; 92:5470–5474. 141. Fletcher RS, Arion D, Borkow G, Wainberg MA, Dmitrienko GI, Parniak MA. Synergistic inhibition of HIV-1 reverse transcriptase DNA polymerase activity and virus replication in vitro by combinations of carboxanilide nonnucleoside compounds. Biochemistry 1995; 34 10106–10112. 142. Baba M, Ito M, Shigeta S, Tanaka H, Miyasaka T, Ubasawa M, et al. Synergistic inhibition of human immunodeficiency virus type 1 replication by 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E- EPU) and azidothymidine in vitro. Antimocrob Agents Chemother 1991; 35:1430–1433. 143. Richman DD, Rosenthal AS, Skoog M, Echner RJ, Chou T-C, Sabo JP, et al. BIRG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine. Antimicrob Agents Chemother 1991; 35:305–308. Page 80 144. Buckheit RW Jr., White EL, Germany-Decker J, Allen LB, Ross LJ, Shannon WM, et al. Cellbased and biochemical analysis of the anti-HIV activity of combinations of 3'-azido-3'-deoxythymidine and analogues of TIBO. Antiviral Chem Chemother 1994; 5:35–42. 145. Chong K-T, Pagano PJ, Hinshaw RR. Bis(heteroacyl)piperazine reverse transcriptase inhibitor in combination with 3'-azido-3'-deoxythymidine or 2',3'-dideoxycytidine synergistically inhibits human immunodeficiency virus type 1 replication in vitro. Antimicrob Agents Chemother 1994; 38:288–293. 146. Brennan TM, Taylor DL, Bridges CG, Leyda JP, Tyms AS. The inhibition of human immunodeficiency virus type 1 in vitro by a non-nucleoside reverse transcriptase inhibitor MKC-442 alone and in combination with other anti-HIV compounds. Antiviral Res 1995; 26:173–187. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_80.html (1 of 2) [4/5/2004 4:53:24 PM]
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netLibrary - eBook Summary Universi
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Structure-based Drug Design 14 Stru
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Document 60. Condra JH, Schleif WA,
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Document 74. Reddy RM, Varney MD, K
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Page 53 and 54: Document Figure 1 (a) Chemical stru
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Page 57 and 58: Document Figure Continued Page 45 r
Page 59 and 60: Document Figure 2 Ribbon diagrams o
Page 61 and 62: Document Figure 3 Overall structure
Page 63 and 64: Document monophosphate analogs whic
Page 65 and 66: Document Analysis of various HIV-1
Page 67 and 68: Document Page 54 Table 2) [12,54].
Page 69 and 70: Document Page 56 It is also attract
Page 71 and 72: Document Table 3 HIV-1 RT Amino Aci
Page 73 and 74: Document ever, once an NNRTI is bou
Page 75 and 76: Document Page 61 now clear that the
Page 77 and 78: Document Page 63 most of the amino
Page 79 and 80: Document Page 65 cal properties of
Page 81 and 82: Document Page 67 Biochemical data s
Page 83 and 84: Document Page 69 determining the me
Page 85 and 86: Document Chris Tantillo. The work i
Page 87 and 88: Document Page 72 16. Goldman ME, Nu
Page 89 and 90: Document 30. Coffin JM. HIV populat
Page 91 and 92: Document 45. Majumadar C, Abbotts J
Page 93 and 94: Document reverse transcriptase inhi
Page 95 and 96: Document 75. Ring CS, Sun E, McKerr
Page 97 and 98: Document 89. Hughes SH, Arnold E, H
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Page 107 and 108: Document 163. Lacey SF, Larder BA.
Page 109 and 110: Document Figure 1 Retroviral lifecy
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Page 113 and 114: Document Page 88 transfer (Figure 3
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Page 117 and 118: Document Page 92 The role of the N-
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Page 121 and 122: Document Page 96 region in the HIV-
Page 123 and 124: Document day junction resolving enz
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Page 127 and 128: Document Page 101 crystallized unde
Page 129 and 130: Document Figure 8 Molscript stereo
Page 131 and 132: Document proposed mechanisms. For e
Page 133 and 134: Document Page 106 on the same ring
Page 135 and 136: Document Page 108 mulate during tre
Page 137 and 138: Document when metals are bound. Fin
Page 139 and 140: Document cubation of phosphotyrosin
Page 141 and 142: Document 4. Vink C, Plasterk RHA. T
Page 143 and 144: Document Page 115 21. Kulkosky J, J
Page 145 and 146: Document 44. Cushman M, Sherman P.
Page 147 and 148: Document 65. Gallay P, Swingler S,
Page 149 and 150: Document 4 Bradykinin Receptor Anta
Page 151 and 152: Document Page 121 Nearly all cells
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Document Page 123 were poorly satis
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Document Page 125 binding site on t
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Document Page 127 The des-Arg 9 for
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Document Page 129 tolerated by the
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Document receptor, it has not yet b
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Document Page 133 This initial stag
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Document Page 135 might be jointly
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Document Page 137 observed for the
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Document Figure 6 Rat and human B2
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Document Page 141 receptor with int
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Document Figure 9 Composition of te
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Document 16. Martorana PA, Kettenba
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Document 39. Mavunkel BJ, Lu Z, Kyl
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Document B. Pharmacology Figure 1 T
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Document We determined the structur
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Document Figure 3 Previously known
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Document large solvent channels and
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Document IV. Drug Design Progressio
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Document position eight from formin
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Document Table 1 Inhibition Data fo
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Document Page 166 As predicated, th
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Document References 1. Parks RE Jr.
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Document 17. Ealick SE, Rule SA, Ca
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Document 6 Structural Implications
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Document Figure 1 A ribbon model of
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Document Page 176 0.43 Å) as the c
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Document Page 178 studies show that
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Document Figure 5 (a) A cut away vi
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Document Page 182 (SAR) model. The
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Document IX. S2' Interactions Page
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Document Figure 6 (a) The pocket of
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Document 5. Willenbrock F, Murphy G
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Document 20. Murphy G, Docherty AJP
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Document Page 189 36. Bode W, Reine
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Document 7 Structure—Function Rel
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Document Figure 1 Reactions catalyz
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Document Figure 2 Structure of lico
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Document Figure 3 (Continued) Page
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Document Important for the validity
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Document Figure 4 Amino acids impor
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Document III. Results and Discussio
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Document Page 202 269, and valine-2
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Document Figure 6 Structure of α h
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Document Page 205 enzyme and of phe
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Document Page 207 sure and the acti
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Document 13. Wilson RC, Krozowski Z
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Document 29. Baker ME. Genealogy of
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Document 46. Ribas dePoplana L, Fot
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Document Page 214 viruses. Specific
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Document Page 218 The catalytic loo
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Document Figure 3 (a) Ternary compl
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Document Figure 5 (a) Staurosporine
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Document protein kinase core is ess
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Document 10. Knighton DR, Zheng J-H
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Document 24. Madhusudan Xuong N-H,
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Document 9 Structural Studies of Al
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Document diverse ARIs have been sho
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Document Figure 3 C α trace of the
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Document Figure 7 Stereo of zopolre
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Document B. Structures Figure 8 Seq
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Document This method was used to sc
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Document 35. Pailhoux EA, Martinez
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Document 10 Structure-Based Design
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Document Cyclotheonamide A (CtA), a
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Document Page 256 The discovery pro
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Document balance its pro- and antic
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Document Page 263 15. Tabernero L,
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Document 31. Kettner C, Shaw E. D-P
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Document Figure 1 The coagulation c
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Document Figure 2 Factor Xa structu
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Document Table 2 Naturally Occurrin
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Document Table 3 Active Site Sequen
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Document Figure 5 Predicted seconda
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Document Lys in the P1 position is
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Document Page 276 In both cases the
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Document Page 278 The n=3 chain len
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Document Figure 10 Proposed model o
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Document Figure 11 dArg-ATS 32-38 m
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Document Figure 12 Modeled fit of S
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Document 36. Leytus SP, Chung DW, K
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Document 54. Broze Jr GJ, Girard TJ
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Document Page 294 70. Seligmann B,
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Document 12 Polypeptide Modulators
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Document Page 297 whereas, calcium
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Document Figure 2 Amino acid sequen
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Document Page 301 domains contribut
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Document Figure 5 Stereo views of 2
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Document A. Chemical Modification P
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Document Page 307 (the exception is
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Document Page 309 site 3 on the sod
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Document Page 314 anemone toxins an
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Document 25. Malpezzi ELA, De Freit
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Document 13 Rational Design of Reni
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Document Page 323 been suggested th
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Document Page 327 this analog inter
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Document plasma. This may arise fro
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Document C. Specificity Figure 4 Th
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Document Figure 5 The S 3 specifici
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Document IV. Rational Drug Design F
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Document 2. Blundell TL, Cooper J,
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Document 17. Szelke M. Chemistry of
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Document 34. Rosenberg SH, Plattner
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Document 48. Powers JC, Harley AD,
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Document Page 343 14 Structural Asp
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Document Figure 4 Amino acid sequen
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Document Figure 5 Schematic stereo
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Document Figure 8 The catalytic mac
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Document Figure 10 Structures of so
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Document From quantitative structur
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Document Page 355 with the tryptoph
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Document Figure 14 The energy profi
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Document Page 359 easily reach the
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Document 35. Davis TL, Roznoski M,
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Document Figure 1 Available drugs f
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Document Table 1 Trypanosomal Targe
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Document Table 2 Three-Dimensional
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Document Figure 2 Glycolysis in blo
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Document II. Three Glycolytic Enzym
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Document Figure 4 Stereoview of sup
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Document Figure 6 Stereoview of NAD
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Document Page 379 For trypanosomal
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Document 5-Methoxytryptamine 19.0 9
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Document Figure 12 Predicted bindin
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Document Page 388 nosine proved to
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Document 15. Carter NS, Fairlamb AH
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Document 30. Kim H, Feil I, Verlind
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Document 49. Michels PAM, Hannaert
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Document 65. João HC, Williams RJP
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Document 84. Verlinde CLMJ, Hol WGJ
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Document 16 Progress in the Design
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Document Table 1 Known Three-Dimens
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Document Page 398 with growth hormo
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Document All effects of the IL-1 fa
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Document Page 405 strands constitut
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Document Figure 4 (a) Stereo diagra
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Document Figure 6 (a) Stereo diagra
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Document Figure 7 (a) Superposition
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Document Page 412 ture is unlike ot
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Document Figure 10 Schematic diagra
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Document Page 416 positions of the
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Document Figure 11 Functional resid
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Document Figure 13 The identified p
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Document B. Interleukin-1 Receptor
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Document Page 423 American Home Pro
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Document Page 425 Antinflammatory D
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Document Page 427 These aromatic di
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Document 5. Dinarello CA. On the Bi
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Document 21. Seckinger P, Lowenthal
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Document 39. Saurat JH, Schfferli J
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Document receptor antagonist into a
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Document 74. Bender PE, Lee JC., ed
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Document 102. Machin PJ, Osbond JM,
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Document 17 Structure and Functiona
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Document Table 1 Approval Indicatio
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Document Page 438 proteins. One pot
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Document II. Type IFNs A great deal
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Document Page 441 sequence of the m
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Document Page 443 that allowed for
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Document Figure 4 Stereo view of IF
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Document Figure 5 Velcro-key model
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Document Figure 6 Proposed receptor
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Document Page 451 with the cytoplas
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Document for directed subcellular t
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Document 13. Stewart HJ, McCann SHE
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Document 33. Szente BE, Johnson HM.
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Document 47. Igarashi K, Garotta G,
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Document Figure 1 A schematic diagr
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Document Page 462 strains of influe
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Document Page 464 could not again b
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Document Figure 3 (a) A MOLSCRIPT [
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Document B. Protein Structure Page
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Document Figure 5 (a) Stereo image
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Document Page 471 molecules in the
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Document hydroxy, and 6 Neu5Ac2en -
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Document Figure 8 Stereo image of t
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Document Page 476 nM, respectively.
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Document Page 478 lished—was asso
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Document VI. Conclusion Page 480 It
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Document 21. Both GW, Sleigh MJ, Co
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Document 40. Drzenick R, Frank H, R
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Document 45. Varghese JN, Laver WG,
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Document 64. Ward CW, Elleman TC, A
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Document 80. Suzuki Y, Sato K, Kiso
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Document Page 486 95. Ryan DM, Tice
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Document Page 488 against most of t
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Document A. The Canyon Page 491 The
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Document Subsequent studies have sh
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Document Page 495 of the RNA and pr
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Document Figure 4 A ribbon diagram
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Document Figure 5 Some compounds wh
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Document Figure 7 HRV14 VP1 hydroph
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Document C. Structure-Activity Rela
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Document Hydrophobicity Requirement
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Document Figure 9 A solvent-accessi
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Document accommodate a variety of d
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Document Figure 10 Possible hydroge
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Document Page 514 sis. Large number
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Document conformational transition
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Document Page 518 The differences b
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Document 10. Mast EE, Harmon MW, Gr
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Document 25. Arnold E, Rossmann MG.
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Document 44. Argos P, Rossmann MG,
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Document 63. Rozhon E, Cox S, Buont
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Document 81. Diana GD, McKinlay MA,
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Document 20 The Integration of Stru
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Document Page 527 function. Iterati
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Document Figure 3 Generation of com
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Document Page 530 screen. For examp
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Document ciency of drug discovery (
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Document Page 533 the reactions are
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Document Page 535 by factoring in a
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Document Page 537 ries, holds the p
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Document 17. Zuckermann RN, Martin
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Document 34. Fei Y-J, Kanai Y, Nuss
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Document 21 Structure-Based Combina
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Document Page 545 protein binding s
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Document Lists of Bonding Fragment
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Document Figure 8 Minimized structu
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Document Page 555 N-acylpyrrolidine
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Document 10. Bobbyer DNA, Goodford
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Document structure. 2. Ligand probe
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Document 30. O'Shea EK, Rutkowski R
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Document 22 Peptidomimetic and Nonp
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Document Figure 1 Examples of nativ
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Document B. Peptidomimetic Drugs: C
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Document Figure 4 Backbone amide bo
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Document 12640-0567a.gif Figure 6 C
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Document Page 569 molecule. A nonco
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Document Figure 17 Nonpeptide drug
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Document Page 595 the MC1 receptor
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Document Figure 22 Protease 3D stru
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Document Page 601 inhibitors 100 [1
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Document Page 603 hydroxymethyl sub
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Document Page 607 scopic studies pr
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Document Page 609 (e.g., thermolysi
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Document (Ser/Thr) peptide 2.9 Å 2
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Document Page 617 Val (131) showed
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Document Figure 32 PTP and PTB 3D s
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Document Acknowledgments Page 620 I
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Document 18. Sawyer TK. In: Peptide
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Document Page 622 Fukuroda T, Fukam
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Document Page 623 53. Bird J, Harpe
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Document 78. Rodriguez M, Crosby R,
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Document MA, Welch KM, Hallak H, Ta
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Document Page 626 SJ, Ogden RC, Red
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Document 97; (e) Fujii I, Nakamura
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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 Page 630 177. (a) Bode W,
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Document Page 631 197. Musil D, Zuc
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Document son AH, Drummond AH, Huxle
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Document 236. (a) Marshall MS. TIBS
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Document 274. (a) Kavanaugh WM, Wil
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Document replacements, 563-565 1-am
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Document inhibitor binding, 323, 33
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Document site, 52, 55, 61 triad, 24
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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 [Interleukin-1] homology w
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Document Kininogen, 119 high molecu
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Document Matrix-metalloproteinase (
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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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