netLibrary - eBook Summary Structure-based Drug Design by ...

More documents

Recommendations

Info

Document Page 479 that 4-guanidino-Neu5Ac2en-resistant mutants can arise from multiple serial passages of virus in MDCK cells in the presence of the inhibitor. It has been demonstrated [104] that almost all of the mutations arise in the hemagglutinin receptor binding site and not on the neuraminidase. These altered HA variants, which have weaker binding to HA receptors, appear to arise as a result of increased inhibition of the neuraminidase by the drug. This is consistent with the earlier proposition that the rate of desialylation of receptor is critically related to the rate of attachment to receptor, for the virus infection and elution. The decreased activity of the neuraminidase by the drug selects HA mutants with decreased binding to receptors. However a drug-resistant neuraminidase mutation has been isolated [103,105] that results in a single active-site residue mutation—with apparently unaltered activity—of glutamic acid 119 to glycine. The crystal structure of this mutant and its complex (Figure 10) with 4-guanidino-Neu5Ac2en has been determined [105] and the structure suggests that the decrease in inhibitor binding arises from the loss of stabilizing interaction with the 4-guanidino group of the drug [72] and alterations in the solvent structure of the active site. This alteration arises from a water molecule that binds near the location of one of the carboxylate oxygens of the glutamic acid in the wild type molecule. The location of the 4-guanidino- Neu5Ac2en drug in the complex with the mutant enzyme is isosteric compared to the drug/wildtype complex [72]. The only differences are the interactions with residue 119. Figure 10 Stereo image of the Glu119Gly Tern/N9 mutant complexed with 4-guanidino-Neu5Ac2en. The inhibitor binds in a similar conformation as with the wild type enzyme. The atom labeled “Wat” represents the water molecule found in the mutant enzyme that assumes the role of the glutamic acid in the wild type enzyme. Nitrogen, oxygen, and carbon atoms are shaded black, dark gray and light gray, respectively. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_479.html (1 of 2) [4/9/2004 12:27:37 AM]
Document VI. Conclusion Page 480 It has now been over a decade since the structure of influenza virus neuraminidase was determined [45,65]. The development of the 4-substituted Neu5ac2en analog inhibitors dates from 1987 when the structure of sialic acid and Neu5Ac2en complexed with neuraminidase were determined to sufficient accuracy to permit modeling of potential inhibitors [66]. The development was a multidisciplinary collaboration of biochemists, crystallographers, molecular modelers, and synthetic chemists and culminated in the synthesis [106] and biological testing of the compounds [91]. Preliminary data on the efficacy of these drugs on humans indicate its effectiveness in both prophylaxis and treatment of the disease [98]. The 4-guanidino compound is in Phase 2 trials (October, 1995). While drug resistance of the virus has been observed in vitro, it will be interesting to see if variants arise in animal studies as they do for Amantidine. This is one of the first rationally designed antiviral drugs to be synthesized and portends well for this methodology to be used as an additional weapon in controling the many pathogens that have plagued humanity for so long. Acknowledgments The author would like to acknowledge Peter Colman, my collaborator in neuraminidase crystallography, Mike Lawrence for the GRID maps shown here and reading this manuscript, Brian Smith for discussions on enzyme mechanisms, Jenny McKimm-Breschkin for discussions on drug resistance, Bert van Donkelaar for technical support, and Paul Davis for computing support. References 1. Kilbourne ED. Influenza. New York: Plenum, 1987. 2. Webster RG, Schafer JR, Suss J, Bean Jr WJ, Kawaoko Y. Evolution and ecology of influenza viruses. In: Hannoun C, et al. eds. Options for the Control of Influenza Virus II. Amsterdam: Excerpta Medica, 1993:177–185. 3. Lamb RA. Genes and proteins of the influenza virus. In: Krug RM, ed. The Influenza Viruses, ed. New York: Plenum, 1989: 1–87. 4. Murphy JS, Bang FB. Observations with the electron microscope on cells of chick chorio-allantoic membrane infected with influenza virus. J Exp Med 1952; 95:259. 5. Compans RW, Dimmock NJ. An electron microscopic study of single-cycle infection of chick embryo fibroblasts by influenza virus. Virology 1969; 39:499. 6. Murphy BR, Webster RG. Orthomyxovirus. In: Fields BN, Knipe DM, eds. Virology. New York: Raven Press, 1990:1091–1152. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_480.html (1 of 2) [4/9/2004 12:27:51 AM]
Page 1 and 2:
netLibrary - eBook Summary Universi
Page 3 and 4:
Structure-based Drug Design 14 Stru
Page 5 and 6:
Document p17, p9, and p7) and repli
Page 7 and 8:
Document Figure 1 Stereo view of th
Page 9 and 10:
Document Figure 2 Schematic represe
Page 11 and 12:
Document TF—transframe, PR—prot
Page 13 and 14:
Document compounds that utilize sim
Page 15 and 16:
Document Page 11 retroviral substra
Page 17 and 18:
Document Page 13 of the active-site
Page 19 and 20:
Document Page 15 Thiazoles are less
Page 21 and 22:
Document Page 17 the resulting chim
Page 23 and 24:
Document http://legacy.netlibrary.c
Page 25 and 26:
Document Figure 5 Stereo view AG134
Page 27 and 28:
Document Page 23 potentially loweri
Page 29 and 30:
Page 31 and 32:
Document Page 27 volume of the acti
Page 33 and 34:
Document Figure 7 Cartoon represent
Page 35 and 36:
Document Figure 8 Cartoon represent
Page 37 and 38:
Document Page 33 sustained in many
Page 39 and 40:
Document 8. Kaplan AH, Zack JA, Kni
Page 41 and 42:
Document 22. Krausslich HG, Ingraha
Page 43 and 44:
Document 35. Kaldor SW, Hammond M,
Page 45 and 46:
Document 47. Tummino PJ, Ferguson D
Page 47 and 48:
Document 60. Condra JH, Schleif WA,
Page 49 and 50:
Document 74. Reddy RM, Varney MD, K
Page 51 and 52:
Document 2 Structural Studies of HI
Page 53 and 54:
Document Figure 1 (a) Chemical stru
Page 55 and 56:
Document dine (3TC), and 2',3'-dide
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
Page 99 and 100:
Document 106. Cirino NM, Cameron CE
Page 101 and 102:
Document 122. Marshall WS, Beaton G
Page 103 and 104:
Document dine) and didanosine (dide
Page 105 and 106:
Document 149. Craig JC, Duncan IB,
Page 107 and 108:
Document 163. Lacey SF, Larder BA.
Page 109 and 110:
Document Figure 1 Retroviral lifecy
Page 111 and 112:
Document Figure 2 In vivo reactions
Page 113 and 114:
Document Page 88 transfer (Figure 3
Page 115 and 116:
Page 117 and 118:
Document Page 92 The role of the N-
Page 119 and 120:
Document Figure 6 Molscript stereo
Page 121 and 122:
Document Page 96 region in the HIV-
Page 123 and 124:
Document day junction resolving enz
Page 125 and 126:
Document -62° for HIV-1 integrase,
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
Page 153 and 154:
Document Page 123 were poorly satis
Page 155 and 156:
Document Page 125 binding site on t
Page 157 and 158:
Document Page 127 The des-Arg 9 for
Page 159 and 160:
Document Page 129 tolerated by the
Page 161 and 162:
Document receptor, it has not yet b
Page 163 and 164:
Document Page 133 This initial stag
Page 165 and 166:
Document Page 135 might be jointly
Page 167 and 168:
Document Page 137 observed for the
Page 169 and 170:
Document Figure 6 Rat and human B2
Page 171 and 172:
Document Page 141 receptor with int
Page 173 and 174:
Page 175 and 176:
Document Figure 9 Composition of te
Page 177 and 178:
Page 179 and 180:
Document 16. Martorana PA, Kettenba
Page 181 and 182:
Document 39. Mavunkel BJ, Lu Z, Kyl
Page 183 and 184:
http://legacy.netlibrary.com/reader
Page 185 and 186:
Document B. Pharmacology Figure 1 T
Page 187 and 188:
Document We determined the structur
Page 189 and 190:
Document Figure 3 Previously known
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Document large solvent channels and
Page 197 and 198:
Document IV. Drug Design Progressio
Page 199 and 200:
Document position eight from formin
Page 201 and 202:
Document Table 1 Inhibition Data fo
Page 203 and 204:
Document Page 166 As predicated, th
Page 205 and 206:
Document References 1. Parks RE Jr.
Page 207 and 208:
Document 17. Ealick SE, Rule SA, Ca
Page 209 and 210:
Document 6 Structural Implications
Page 211 and 212:
Document Figure 1 A ribbon model of
Page 213 and 214:
Page 215 and 216:
Document Page 176 0.43 Å) as the c
Page 217 and 218:
Document Page 178 studies show that
Page 219 and 220:
Document Figure 5 (a) A cut away vi
Page 221 and 222:
Document Page 182 (SAR) model. The
Page 223 and 224:
Document IX. S2' Interactions Page
Page 225 and 226:
Document Figure 6 (a) The pocket of
Page 227 and 228:
Document 5. Willenbrock F, Murphy G
Page 229 and 230:
Document 20. Murphy G, Docherty AJP
Page 231 and 232:
Document Page 189 36. Bode W, Reine
Page 233 and 234:
Document 7 Structure—Function Rel
Page 235 and 236:
Document Figure 1 Reactions catalyz
Page 237 and 238:
Document Figure 2 Structure of lico
Page 239 and 240:
Document Figure 3 (Continued) Page
Page 241 and 242:
Document Important for the validity
Page 243 and 244:
Document Figure 4 Amino acids impor
Page 245 and 246:
Document III. Results and Discussio
Page 247 and 248:
Document Page 202 269, and valine-2
Page 249 and 250:
Document Figure 6 Structure of α h
Page 251 and 252:
Document Page 205 enzyme and of phe
Page 253 and 254:
Document Page 207 sure and the acti
Page 255 and 256:
Document 13. Wilson RC, Krozowski Z
Page 257 and 258:
Document 29. Baker ME. Genealogy of
Page 259 and 260:
Document 46. Ribas dePoplana L, Fot
Page 261 and 262:
Page 263 and 264:
Document Page 214 viruses. Specific
Page 265 and 266:
Document Figure 1 (Continued) this
Page 267 and 268:
Document Page 218 The catalytic loo
Page 269 and 270:
Document Page 220 conserved substra
Page 271 and 272:
Document Figure 3 (a) Ternary compl
Page 273 and 274:
Document Figure 5 (a) Staurosporine
Page 275 and 276:
Document protein kinase core is ess
Page 277 and 278:
Document 10. Knighton DR, Zheng J-H
Page 279 and 280:
Document 24. Madhusudan Xuong N-H,
Page 281 and 282:
Document 9 Structural Studies of Al
Page 283 and 284:
Document diverse ARIs have been sho
Page 285 and 286:
Document Figure 3 C α trace of the
Page 287 and 288:
Document Figure 4 Surface represent
Page 289 and 290:
Page 291 and 292:
Document Figure 7 Stereo of zopolre
Page 293 and 294:
Document B. Structures Figure 8 Seq
Page 295 and 296:
Document This method was used to sc
Page 297 and 298:
Document 2. Lee AYW, Chung SK, Chun
Page 299 and 300:
Document 18. Wilson DK, Tarle I, Pe
Page 301 and 302:
Document 35. Pailhoux EA, Martinez
Page 303 and 304:
Document 10 Structure-Based Design
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Document Cyclotheonamide A (CtA), a
Page 313 and 314:
Document Page 256 The discovery pro
Page 315 and 316:
Page 317 and 318:
Document et al. [21]). Among these
Page 319 and 320:
Document balance its pro- and antic
Page 321 and 322:
Document Page 263 15. Tabernero L,
Page 323 and 324:
Document 31. Kettner C, Shaw E. D-P
Page 325 and 326:
Document Figure 1 The coagulation c
Page 327 and 328:
Document Figure 2 Factor Xa structu
Page 329 and 330:
Document Table 2 Naturally Occurrin
Page 331 and 332:
Document Table 3 Active Site Sequen
Page 333 and 334:
Document Figure 5 Predicted seconda
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
Page 341 and 342:
Document Figure 10 Proposed model o
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
Page 349 and 350:
Page 351 and 352:
Document Page 288 Additionally, the
Page 353 and 354:
Document Page 290 5. Kaiser B, Haup
Page 355 and 356:
Document Page 291 21. Davie EW, Fuj
Page 357 and 358:
Document 36. Leytus SP, Chung DW, K
Page 359 and 360:
Document 54. Broze Jr GJ, Girard TJ
Page 361 and 362:
Document Page 294 70. Seligmann B,
Page 363 and 364:
Document 12 Polypeptide Modulators
Page 365 and 366:
Document Page 297 whereas, calcium
Page 367 and 368:
Document Figure 2 Amino acid sequen
Page 369 and 370:
Document Page 301 domains contribut
Page 371 and 372:
Document Figure 5 Stereo views of 2
Page 373 and 374:
Document A. Chemical Modification P
Page 375 and 376:
Document Page 307 (the exception is
Page 377 and 378:
Document Page 309 site 3 on the sod
Page 379 and 380:
Page 381 and 382:
Document Page 312 In peptide—prot
Page 383 and 384:
Document Page 314 anemone toxins an
Page 385 and 386:
Document 5. Packer M, Gheorghiade M
Page 387 and 388:
Document 25. Malpezzi ELA, De Freit
Page 389 and 390:
Document 42. Catterall WA, Beress L
Page 391 and 392:
Document 60. Pennington MW, Zadenbe
Page 393 and 394:
Document 76. Gould AR, Mabbutt BC,
Page 395 and 396:
Document 13 Rational Design of Reni
Page 397 and 398:
Document Page 323 been suggested th
Page 399 and 400:
Document Figure 2 A schematic diagr
Page 401 and 402:
Document Page 327 this analog inter
Page 403 and 404:
Document Page 329 binding involves
Page 405 and 406:
Document plasma. This may arise fro
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
Page 417 and 418:
Document 34. Rosenberg SH, Plattner
Page 419 and 420:
Document 48. Powers JC, Harley AD,
Page 421 and 422:
Document Page 343 14 Structural Asp
Page 423 and 424:
Document Figure 2 The reaction cata
Page 425 and 426:
Document Figure 4 Amino acid sequen
Page 427 and 428:
Document Figure 5 Schematic stereo
Page 429 and 430:
Document Figure 8 The catalytic mac
Page 431 and 432:
Document Figure 10 Structures of so
Page 433 and 434:
Document From quantitative structur
Page 435 and 436:
Document Page 355 with the tryptoph
Page 437 and 438:
Document Figure 14 The energy profi
Page 439 and 440:
Document Page 359 easily reach the
Page 441 and 442:
Document Page 361 2. Guldberg H, Ma
Page 443 and 444:
Document Page 362 19. Lotta T, Vidg
Page 445 and 446:
Document 35. Davis TL, Roznoski M,
Page 447 and 448:
Page 449 and 450:
Document Figure 1 Available drugs f
Page 451 and 452:
Document Table 1 Trypanosomal Targe
Page 453 and 454:
Document Table 2 Three-Dimensional
Page 455 and 456:
Document Figure 2 Glycolysis in blo
Page 457 and 458:
Document II. Three Glycolytic Enzym
Page 459 and 460:
Document Figure 4 Stereoview of sup
Page 461 and 462:
Document Figure 6 Stereoview of NAD
Page 463 and 464:
Document Page 376 was recently solv
Page 465 and 466:
Document Because there are no known
Page 467 and 468:
Document Page 379 For trypanosomal
Page 469 and 470:
Page 471 and 472:
Document Because there are tens of
Page 473 and 474:
Document 5-Methoxytryptamine 19.0 9
Page 475 and 476:
Document Figure 11 Two-dimensional
Page 477 and 478:
Document Figure 12 Predicted bindin
Page 479 and 480:
Document Page 388 nosine proved to
Page 481 and 482:
Document 15. Carter NS, Fairlamb AH
Page 483 and 484:
Document 30. Kim H, Feil I, Verlind
Page 485 and 486:
Document 49. Michels PAM, Hannaert
Page 487 and 488:
Document 65. João HC, Williams RJP
Page 489 and 490:
Document 84. Verlinde CLMJ, Hol WGJ
Page 491 and 492:
Document 16 Progress in the Design
Page 493 and 494:
Document Table 1 Known Three-Dimens
Page 495 and 496:
Document Page 398 with growth hormo
Page 497 and 498:
Document All effects of the IL-1 fa
Page 499 and 500:
Document has a single membrane-span
Page 501 and 502:
Document Figure 2 Structural alignm
Page 503 and 504:
Document Page 405 strands constitut
Page 505 and 506:
Document Figure 4 (a) Stereo diagra
Page 507 and 508:
Document Figure 6 (a) Stereo diagra
Page 509 and 510:
Document Figure 7 (a) Superposition
Page 511 and 512:
Document Page 412 ture is unlike ot
Page 513 and 514:
Document Figure 10 Schematic diagra
Page 515 and 516:
Document Page 416 positions of the
Page 517 and 518:
Document Figure 11 Functional resid
Page 519 and 520:
Document Figure 13 The identified p
Page 521 and 522:
Document B. Interleukin-1 Receptor
Page 523 and 524:
Document Page 423 American Home Pro
Page 525 and 526:
Document Page 425 Antinflammatory D
Page 527 and 528:
Document Page 427 These aromatic di
Page 529 and 530:
Document 5. Dinarello CA. On the Bi
Page 531 and 532:
Document 21. Seckinger P, Lowenthal
Page 533 and 534:
Document 39. Saurat JH, Schfferli J
Page 535 and 536:
Document receptor antagonist into a
Page 537 and 538:
Document 74. Bender PE, Lee JC., ed
Page 539 and 540:
Document 102. Machin PJ, Osbond JM,
Page 541 and 542: Document 17 Structure and Functiona
Page 543 and 544: Document Table 1 Approval Indicatio
Page 545 and 546: Document Page 438 proteins. One pot
Page 547 and 548: Document II. Type IFNs A great deal
Page 549 and 550: Document Page 441 sequence of the m
Page 551 and 552: Document Page 443 that allowed for
Page 553 and 554: Document Figure 4 Stereo view of IF
Page 555 and 556: Document Figure 5 Velcro-key model
Page 557 and 558: Document Figure 6 Proposed receptor
Page 559 and 560: Document Page 451 with the cytoplas
Page 561 and 562: Document for directed subcellular t
Page 563 and 564: Document 13. Stewart HJ, McCann SHE
Page 565 and 566: Document 33. Szente BE, Johnson HM.
Page 567 and 568: Document 47. Igarashi K, Garotta G,
Page 569 and 570: http://legacy.netlibrary.com/reader
Page 571 and 572: Document Figure 1 A schematic diagr
Page 573 and 574: Document Page 462 strains of influe
Page 575 and 576: Document Page 464 could not again b
Page 577 and 578: Document Figure 3 (a) A MOLSCRIPT [
Page 579 and 580: Document B. Protein Structure Page
Page 581 and 582: Document Figure 5 (a) Stereo image
Page 583 and 584: Document Page 471 molecules in the
Page 585 and 586: Document hydroxy, and 6 Neu5Ac2en -
Page 587 and 588: Document Figure 8 Stereo image of t
Page 589 and 590: Document Page 476 nM, respectively.
Page 591: Document Page 478 lished—was asso
Page 595 and 596: Document 21. Both GW, Sleigh MJ, Co
Page 597 and 598: Document 40. Drzenick R, Frank H, R
Page 599 and 600: Document 45. Varghese JN, Laver WG,
Page 601 and 602: Document 64. Ward CW, Elleman TC, A
Page 603 and 604: Document 80. Suzuki Y, Sato K, Kiso
Page 605 and 606: Document Page 486 95. Ryan DM, Tice
Page 607 and 608: Document Page 488 against most of t
Page 609 and 610: Document http://legacy.netlibrary.c
Page 611 and 612: Document A. The Canyon Page 491 The
Page 613 and 614: Document Subsequent studies have sh
Page 615 and 616: Document Page 495 of the RNA and pr
Page 617 and 618: Document Figure 4 A ribbon diagram
Page 619 and 620: Document Figure 5 Some compounds wh
Page 621 and 622: Document Figure 7 HRV14 VP1 hydroph
Page 623 and 624: Document C. Structure-Activity Rela
Page 629 and 630: Document Hydrophobicity Requirement
Page 631 and 632: Document Figure 9 A solvent-accessi
Page 633 and 634: Document accommodate a variety of d
Page 635 and 636: Document Figure 10 Possible hydroge
Page 637 and 638: Document Page 514 sis. Large number
Page 639 and 640: Document conformational transition
Page 641 and 642: Document Page 518 The differences b
Page 643 and 644:
Document 10. Mast EE, Harmon MW, Gr
Page 645 and 646:
Document 25. Arnold E, Rossmann MG.
Page 647 and 648:
Document 44. Argos P, Rossmann MG,
Page 649 and 650:
Document 63. Rozhon E, Cox S, Buont
Page 651 and 652:
Document 81. Diana GD, McKinlay MA,
Page 653 and 654:
Document 20 The Integration of Stru
Page 655 and 656:
Document Page 527 function. Iterati
Page 657 and 658:
Document Figure 3 Generation of com
Page 659 and 660:
Document Page 530 screen. For examp
Page 661 and 662:
Document ciency of drug discovery (
Page 663 and 664:
Document Page 533 the reactions are
Page 665 and 666:
Document Page 535 by factoring in a
Page 667 and 668:
Document Page 537 ries, holds the p
Page 669 and 670:
Document 17. Zuckermann RN, Martin
Page 671 and 672:
Document 34. Fei Y-J, Kanai Y, Nuss
Page 673 and 674:
Document 21 Structure-Based Combina
Page 675 and 676:
Page 677 and 678:
Document Page 545 protein binding s
Page 679 and 680:
Page 681 and 682:
Document Figure 3 (a) Stereo view o
Page 683 and 684:
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
Page 695 and 696:
Document 30. O'Shea EK, Rutkowski R
Page 697 and 698:
Document 22 Peptidomimetic and Nonp
Page 699 and 700:
Document Figure 1 Examples of nativ
Page 701 and 702:
Document B. Peptidomimetic Drugs: C
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
Page 711 and 712:
Document Figure 9 Peptide scaffold-
Page 713 and 714:
Document Figure 11 Protease-targete
Page 715 and 716:
Document Figure 12 Peptide scaffold
Page 717 and 718:
Page 719 and 720:
Document Figure 14 Signal-transduct
Page 721 and 722:
Page 723 and 724:
Page 725 and 726:
Document Figure 17 Nonpeptide drug
Page 727 and 728:
Page 729 and 730:
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 737 and 738:
Page 739 and 740:
Document Figure 22 Protease 3D stru
Page 741 and 742:
Document Page 601 inhibitors 100 [1
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 751 and 752:
Page 753 and 754:
Page 755 and 756:
Document (Ser/Thr) peptide 2.9 Å 2
Page 757 and 758:
Page 759 and 760:
Page 761 and 762:
Document Page 617 Val (131) showed
Page 763 and 764:
Document Figure 32 PTP and PTB 3D s
Page 765 and 766:
Document Acknowledgments Page 620 I
Page 767 and 768:
Document 18. Sawyer TK. In: Peptide
Page 769 and 770:
Document Page 622 Fukuroda T, Fukam
Page 771 and 772:
Document Page 623 53. Bird J, Harpe
Page 773 and 774:
Document 78. Rodriguez M, Crosby R,
Page 775 and 776:
Document MA, Welch KM, Hallak H, Ta
Page 777 and 778:
Document Page 626 SJ, Ogden RC, Red
Page 779 and 780:
Document 97; (e) Fujii I, Nakamura
Page 781 and 782:
Document Med Biol 1991; 306:9-21; (
Page 783 and 784:
Document Page 629 ML, Clare M, Decr
Page 785 and 786:
Document Page 630 177. (a) Bode W,
Page 787 and 788:
Document Page 631 197. Musil D, Zuc
Page 789 and 790:
Document son AH, Drummond AH, Huxle
Page 791 and 792:
Document 236. (a) Marshall MS. TIBS
Page 793 and 794:
Page 795 and 796:
Document 274. (a) Kavanaugh WM, Wil
Page 797 and 798:
Document replacements, 563-565 1-am
Page 799 and 800:
Document inhibitor binding, 323, 33
Page 801 and 802:
Document site, 52, 55, 61 triad, 24
Page 803 and 804:
Document factors, 247 Combination t
Page 805 and 806:
Document Cyclotheonamide A (CtA), 2
Page 807 and 808:
Document D ddI, 152 tumour necrosis
Page 809 and 810:
Document antistasin peptides, 281 c
Page 811 and 812:
Document fragment-based programs, 5
Page 813 and 814:
Document [Human immunodeficiency vi
Page 815 and 816:
Document overview, 103-104, 108-109
Page 817 and 818:
Document [Inhibitors] 2-((3,4-dihyd
Page 819 and 820:
Document antagonistic activity, 416
Page 821 and 822:
Document [Interleukin-1] homology w
Page 823 and 824:
Document Kininogen, 119 high molecu
Page 825 and 826:
Document Matrix-metalloproteinase (
Page 827 and 828:
Document RT inhibitor, 41, 56 Nonpe
Page 829 and 830:
Document Phosphoglycerate kinase (P
Page 831:
Document [Protease targets] serinyl
show all

netLibrary - eBook Summary Structure-based Drug Design by ...

Create successful ePaper yourself

Delete template?

Save as template?