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Document Figure 10 Peptide scaffold- and nonpeptide template-based design strategies: somatostatin agonist and substance-P (NK 1) antagonists resolution 3D structures of bacteriorhodopsin or rhodopsin, see below) the development of Page 574 pharmacophore models using the hierarchial approach in peptide rarrow.gif peptidomimetic structurebased drug design (see above, Figure 3) remains quite promising to creative science. Indeed, targetedreceptor screening of synthetic chemical libraries of highly modified peptide molecules (e.g., Nsubstituted Gly “peptoids” [21] is rapidly expanding our database of structurally diverse ligands. Such structurally unique lead compounds will provide the opportunity for further pharmacophore modeling strategies to be used in the discovery of novel agonists or antagonists at GPCR and other receptor types. B. Peptidomimetics: Protease Inhibitors Specific examples of peptidomimetics which illustrate peptide scaffold- and nonpeptide templatedirected drug-design strategies as applied to protease in- http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_574.html (1 of 2) [4/9/2004 1:09:58 AM]
Document Figure 11 Protease-targeted peptidomimetics derived by ligand structure-based drug design http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_575.html [4/9/2004 1:10:57 AM] Page 575
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netLibrary - eBook Summary Universi
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Structure-based Drug Design 14 Stru
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Document Page 15 Thiazoles are less
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Document Figure 7 Cartoon represent
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Document Page 33 sustained in many
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Document 8. Kaplan AH, Zack JA, Kni
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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 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 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 Figure 8 Molscript stereo
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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 4. Vink C, Plasterk RHA. T
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Document Page 115 21. Kulkosky J, J
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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 125 binding site on t
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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 Page 220 conserved substra
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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 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 18. Wilson DK, Tarle I, Pe
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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 et al. [21]). Among these
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Document balance its pro- and antic
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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 Lys in the P1 position is
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Document 12 Polypeptide Modulators
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Document A. Chemical Modification P
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Document 13 Rational Design of Reni
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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 17. Szelke M. Chemistry of
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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 Table 1 Trypanosomal Targe
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Document II. Three Glycolytic Enzym
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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 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 39. Saurat JH, Schfferli J
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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 Page 441 sequence of the m
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Document Figure 5 Velcro-key model
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Document Page 462 strains of influe
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Document B. Protein Structure Page
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Document hydroxy, and 6 Neu5Ac2en -
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Document Page 476 nM, respectively.
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Document VI. Conclusion Page 480 It
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Document 64. Ward CW, Elleman TC, A
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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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Page 673 and 674: Document 21 Structure-Based Combina
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Page 677 and 678: Document Page 545 protein binding s
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Page 685 and 686: Document Lists of Bonding Fragment
Page 687 and 688: Document Figure 8 Minimized structu
Page 689 and 690: Document Page 555 N-acylpyrrolidine
Page 691 and 692: Document 10. Bobbyer DNA, Goodford
Page 693 and 694: Document structure. 2. Ligand probe
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Page 697 and 698: Document 22 Peptidomimetic and Nonp
Page 699 and 700: Document Figure 1 Examples of nativ
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Page 703 and 704: Document Figure 4 Backbone amide bo
Page 705 and 706: Document 12640-0567a.gif Figure 6 C
Page 707 and 708: Document Page 569 molecule. A nonco
Page 709 and 710: Document cases, a pharmacophore mod
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Page 715 and 716: Document Figure 12 Peptide scaffold
Page 719 and 720: Document Figure 14 Signal-transduct
Page 725 and 726: Document Figure 17 Nonpeptide drug
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Page 731 and 732: Document Page 591 often suggest tha
Page 733 and 734: Document Page 593 versus antagonist
Page 735 and 736: Document Page 595 the MC1 receptor
Page 739 and 740: Document Figure 22 Protease 3D stru
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Page 743 and 744: Document Page 603 hydroxymethyl sub
Page 745 and 746: Document Page 605 For other serinyl
Page 747 and 748: Document Page 607 scopic studies pr
Page 749 and 750: Document Page 609 (e.g., thermolysi
Page 755 and 756: Document (Ser/Thr) peptide 2.9 Å 2
Page 761 and 762: 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 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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