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Document for use in the treatment of chronic CHF. This chapter describes how this development is being tackled using the approach of structure-<strong>based</strong> drug design. A. Related Sea Anemone Toxins Page 298 Anthopleurin-A is a member of a family of sea anemone polypeptides [24] (Figure 2) that is steadily increasing in number. These polypeptides have been classified into two groups, designated Types 1 and 2 [27], which are similar with respect to the locations of their disulfide bridges and a number of residues thought to play a role in biological activity or maintenance of the tertiary structure [24,27], but are distinguishable on the basis of sequence similarity (>>60% within each type but
Document Figure 2 Amino acid sequences of Type 1 sea anemone polypeptides. The residue numbering system is <strong>based</strong> on the sequences of AP-A and AP-B. Literature references are from Norton [24], except in the case of recently published sequences for Bc III [25], Bg II and Bg III [26]. Identical residues are shaded in grey and conserved residues are boxed. The sequences of Bg II and Bg III around residue 28 could also be aligned to bring the Gly-Cys sequence into register with the other toxins if the Arg were treated as an insertion. Toxins are named in this figure according to their genus and species; common names relevant to the text are Ax I = AP-A; Ax II = AP-B; As Ia = ATX Ia. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_299.html [4/5/2004 5:19:48 PM] Page 299
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Document Page 33 sustained in many
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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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Document 2 Structural Studies of HI
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Document Figure 1 (a) Chemical stru
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Document dine (3TC), and 2',3'-dide
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Document Figure Continued Page 45 r
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Document Figure 2 Ribbon diagrams o
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Document Figure 3 Overall structure
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Document monophosphate analogs whic
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Document Analysis of various HIV-1
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Document Page 54 Table 2) [12,54].
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Document Page 56 It is also attract
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Document Table 3 HIV-1 RT Amino Aci
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Document ever, once an NNRTI is bou
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Document Page 61 now clear that the
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Document Page 63 most of the amino
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Document Page 65 cal properties of
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Document Page 67 Biochemical data s
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Document Page 69 determining the me
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Document Chris Tantillo. The work i
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Document Page 72 16. Goldman ME, Nu
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Document 30. Coffin JM. HIV populat
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Document 45. Majumadar C, Abbotts J
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Document reverse transcriptase inhi
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Document 75. Ring CS, Sun E, McKerr
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Document 89. Hughes SH, Arnold E, H
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Document 106. Cirino NM, Cameron CE
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Document 122. Marshall WS, Beaton G
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Document dine) and didanosine (dide
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Document 149. Craig JC, Duncan IB,
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Document 163. Lacey SF, Larder BA.
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Document Figure 1 Retroviral lifecy
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Document Figure 2 In vivo reactions
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Document Page 88 transfer (Figure 3
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Document Page 92 The role of the N-
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Document Figure 6 Molscript stereo
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Document Page 96 region in the HIV-
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Document day junction resolving enz
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Document -62° for HIV-1 integrase,
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Document Page 101 crystallized unde
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Document proposed mechanisms. For e
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Document Page 106 on the same ring
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Document Page 108 mulate during tre
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Document when metals are bound. Fin
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Document cubation of phosphotyrosin
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Document 65. Gallay P, Swingler S,
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Document 4 Bradykinin Receptor Anta
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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 20. Murphy G, Docherty AJP
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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 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 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 5 (a) Staurosporine
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Document protein kinase core is ess
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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 4 Surface represent
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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 Cyclotheonamide A (CtA), a
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Page 319 and 320: Document balance its pro- and antic
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Page 323 and 324: Document 31. Kettner C, Shaw E. D-P
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Page 327 and 328: Document Figure 2 Factor Xa structu
Page 329 and 330: Document Table 2 Naturally Occurrin
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Page 335 and 336: Document Lys in the P1 position is
Page 337 and 338: Document Page 276 In both cases the
Page 339 and 340: Document Page 278 The n=3 chain len
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Page 343 and 344: Document Figure 11 dArg-ATS 32-38 m
Page 345 and 346: Document Figure 12 Modeled fit of S
Page 347 and 348: Document Page 285 number of x-ray s
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Page 363 and 364: Document 12 Polypeptide Modulators
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Page 373 and 374: Document A. Chemical Modification P
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Page 383 and 384: Document Page 314 anemone toxins an
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Page 389 and 390: Document 42. Catterall WA, Beress L
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Page 395 and 396: Document 13 Rational Design of Reni
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Page 407 and 408: Document C. Specificity Figure 4 Th
Page 409 and 410: Document Figure 5 The S 3 specifici
Page 411 and 412: Document IV. Rational Drug Design F
Page 413 and 414: Document 2. Blundell TL, Cooper J,
Page 415 and 416: 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 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 Figure 14 The energy profi
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Document Page 359 easily reach the
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Document Table 1 Trypanosomal Targe
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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 Because there are tens of
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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 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 Figure 2 Structural alignm
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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 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 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 Page 527 function. Iterati
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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 537 ries, holds the p
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Document 17. Zuckermann RN, Martin
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Document 21 Structure-Based Combina
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Document Page 545 protein binding s
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Document Page 555 N-acylpyrrolidine
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Document 10. Bobbyer DNA, Goodford
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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 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 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 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 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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