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Bioactive Conformation I pp 259–296Cite as

Exploiting Ligand and Receptor Adaptability in Rational Drug Design Using Dynamics and Structure-Based Strategies

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Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 272))

Abstract

Interactions between a biological macromolecule and a small molecule ligand involve intricate recognition events which are strongly influenced by both structure and dynamics factors. The ligand and receptor must mutually fit and adapt to each other to form a strong complex, and detailed knowledge of these factors would certainly aid drug design efforts. This work describes our experience in the characterization and exploitation of these properties within the context of two medicinal chemistry programs that targeted the essential protease enzymes of the human cytomegalovirus (HCMV) and the hepatitis C virus (HCV). Central to the rational use of such data was the qualitative elucidation of the binding parameters that defined modes/roles of each substituent of the ligands. This required the development of dynamics- and structure-based strategies that logically considered data from structure–activity relationships, NMR spectroscopy, computational chemistry, and X-ray crystallography. An important emphasis was made to monitor the relationship between inhibitor activity and ligand flexibility using 13C NMR T 1 relaxation data, within the context of promoting the bioactive conformation as a drug design tool. Besides these methods which focused on data from the ligand perspective, interesting ligand-induced adaptive features of the receptors were also observed, and their impacts on drug design were explored.

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Abbreviations

NMR:

nuclear magnetic resonance

13C T 1 :

13C NMR spin lattice relaxation

IC50 :

inhibition constant at 50% concentration

HCV:

hepatitis C virus

HCMV:

human cytomegalovirus

C-terminal:

C-terminus of a peptide chain

N-terminal:

N-terminus of a peptide chain

NOESY:

NMR nuclear Overhauser effect spectroscopy

ROESY:

NMR rotating-frame nuclear Overhauser effect spectroscopy

AIDS:

auto-immune deficiency syndrome

HSV:

herpes simplex virus

DLB:

NMR differential line broadening

SAR:

structure-activity relationship

NS:

non-structural

HSQC:

NMR heteronuclear single-quantum correlation

References

  1. Mocarski ES Jr (1995) In: Fields BN (ed) Virology 2. Lippincott-Raven, Philadelphia, PA, pp 2447–2492

    Google Scholar 

  2. Britt WJ, Alford CA (1995) In: Fields BN (ed) Virology 2. Lippincott-Raven, Philadelphia, PA, pp 2493–2525

    Google Scholar 

  3. Gibson W, Welch AR, Hall MRT (1994) Perspect Drug Discov Des 2:413

    Article  Google Scholar 

  4. Gao M, Matusick-Kumar L, Hurlburt W, DiTusa SF, Newcomb WW, Brown JC, McCann PJ III, Deckman I, Colonno RJ (1994) J Virol 68:3702

    CAS  Google Scholar 

  5. Preston VG, Coates JAV, Rixon FJ (1983) J Virol 45:1056

    CAS  Google Scholar 

  6. Matusick-Kumar L, McCann PJ III, Robertson BJ, Newcomb WW, Brown JC, Gao M (1995) J Virol 69:113

    Google Scholar 

  7. Casjens S, King J (1975) Annu Rev Biochem 44:555

    Article  CAS  Google Scholar 

  8. Tong L, Qian C, Massariol M-J, Bonneau PR, Cordingley MG, Lagacé L (1996) Nature 383:272

    Article  CAS  Google Scholar 

  9. Qiu X, Culp JS, DiLella AG, Hellmig B, Hoog SS, Janson CA, Smith WW, Abdel-Meguid SS (1996) Nature 383:275

    Article  CAS  Google Scholar 

  10. Shieh H-S, Kurumbail RG, Stevens AM, Stegeman RA, Sturman EJ, Pak JY, Wittwer AJ, Palmier MO, Wiegand RC, Holwerda BC, Stallings WC (1996) Nature 383:279

    Article  CAS  Google Scholar 

  11. Chen P, Tsuge H, Almassy RJ, Gribskov CL, Katoh S, Vanderpool DL, Margosiak SA, Pinko C, Matthews DA, Kan C-C (1996) Cell 86:835

    Article  CAS  Google Scholar 

  12. Margosiak SA, Vanderpool DL, Sisson W, Pinko C, Kan C-C (1996) Biochemistry 35:5300

    Article  CAS  Google Scholar 

  13. Darke PL, Cole JL, Waxman L, Hall DL, Sardana MK, Kuo LC (1996) J Biol Chem 271:7445

    Article  CAS  Google Scholar 

  14. Bonneau PR, Grand-Maître C, Greenwood DJ, Lagacé L, LaPlante SR, Massariol M-J, Ogilvie WW, O'Meara JA, Kawai SH (1997) Biochemistry 36:12644

    Article  CAS  Google Scholar 

  15. LaPlante SR, Bonneau P, Aubry N, Cameron DR, Déziel R, Grand-Maître C, Plouffe C, Tong L, Kawai SH (1999) J Am Chem Soc 121:2974

    Article  CAS  Google Scholar 

  16. LaPlante SR, Aubry N, Bonneau PR, Cameron DR, Lagacé L, Massariol M-J, Montpetit H, Plouffe C, Kawai SH, Fulton BD, Chen ZG, Ni F (1998) Biochemistry 37:9793

    Article  CAS  Google Scholar 

  17. Schechter J, Berger A (1970) Philos Trans R Soc London, Ser B 257:249

    Article  Google Scholar 

  18. Sardana VV, Wolfgang JA, Veloski CA, Long WJ, Legrow K, Wolanski B, Emini EA, LaFemina RL (1994) J Biol Chem 269:14337

    CAS  Google Scholar 

  19. LaFemina RL, Bakshi K, Long WJ, Pramanik B, Veloski CA, Wolanski BS, Marcy AI, Hazuda DJ (1996) J Virol 70:4819

    CAS  Google Scholar 

  20. Ni F (1994) Prog NMR Spectrosc 26:517

    Article  CAS  Google Scholar 

  21. Fersht A (1985) Enzyme Structure and Mechanisms. 2nd edn. Freeman and Co, New York

    Google Scholar 

  22. Polgár L (ed) (1989) Mechanisms of Protease Action. Chap. 3. CRC Press Inc, Boca Raton, FL

    Google Scholar 

  23. Hedstrom L (2002) Chem Rev 102:4501

    Article  CAS  Google Scholar 

  24. Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison WR, Fischer KP, Churchill TA, Lakey JRT, Tyrrell DLJ, Kneteman NM (2001) Nat Med 7:927

    Article  CAS  Google Scholar 

  25. Ogilvie WW, Bailey M, Poupart M-A, Abraham A, Bhavsar A, Bonneau PR, Bordeleau J, Bousquet Y, Chabot C, Duceppe J-S, Fazal G, Goulet S, Grand-Maître C, Guse I, Halmos T, Lavallée P, Leach M, Malenfant E, O'Meara JA, Plante R, Plouffe C, Poirier M, Soucy F, Yoakim C, Déziel R (1998) J Med Chem 40:4113

    Article  Google Scholar 

  26. LaPlante SR, Cameron DR, Aubry N, Bonneau PR, Déziel R, Grand-Maître C, Ogilvie WW, Kawai SH (1998) Angew Chem Int Ed Engl 37:2729

    Article  CAS  Google Scholar 

  27. Tong L, Qian C, Massariol M-J, Déziel R, Yoakim C, Lagacé L (1998) Nature Struct Biol 5:819

    Article  CAS  Google Scholar 

  28. Cao Y, Musah RA, Wilcox SK, Goodin DB, McRee DE (1998) Protein Sci 7:72

    Article  CAS  Google Scholar 

  29. Wolfenden R (1972) Acc Chem Res 5:10

    Article  CAS  Google Scholar 

  30. Wolfenden R (1976) Annu Rev Biophys 5:271

    Article  CAS  Google Scholar 

  31. Yoakim C, Ogilvie WW, Cameron DR, Chabot C, Guse I, Haché B, Naud J, O'Meara JA, Plante R, Déziel R (1998) J Med Chem 41:2882

    Article  CAS  Google Scholar 

  32. Déziel R, Malenfant E (1998) Bioorg Med Chem Lett 8:1437

    Article  Google Scholar 

  33. Yoakim C, Ogilvie W, Cameron DR, Chabot C, Grand-Maître C, Guse I, Haché B, Kawai SH, Naud J, O'Meara JA, Plante R, Déziel R (1998) Antiviral Chem Chemother 9:379

    CAS  Google Scholar 

  34. Borthwick AD, Weingarten G, Haley TM, Tomaszewski M, Wand W, Hu Z, Bédard J, Jin H, Yuen L, Mansour TS (1998) Bioorg Med Chem Lett 8:365

    Article  CAS  Google Scholar 

  35. Bonneau PR, Hasani F, Plouffe C, Malenfant E, LaPlante SR, Guse I, Ogilvie WW, Plante R, Davidson WC, Hopkins JL, Morelock MG, Cordingley MG, Déziel R (1999) J Am Chem Soc 121:2965

    Article  CAS  Google Scholar 

  36. LaPlante SR, Llinàs-Brunet M (2005) Curr Med Chem Antiinfective Agents 4:111

    Article  CAS  Google Scholar 

  37. Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Science 244:359

    Article  CAS  Google Scholar 

  38. Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker A G, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE (1989) Science 244:362

    Article  CAS  Google Scholar 

  39. Di Bisceglie AM (1998) Lancet 351:351

    Article  Google Scholar 

  40. World Health Organization (1999) J Virol Hepat 6:35

    Article  Google Scholar 

  41. Chander G, Sulkowski MS, Jenckes MW, Torbenson MS, Herlong HF, Bass EB, Gebo KA (2002) Hepatology 36:S135

    Article  Google Scholar 

  42. Tan S-L, Pause A, Shi Y, Sonenberg N (2002) Nature Rev Drug Discov 1:867

    Article  CAS  Google Scholar 

  43. Di Bisceglie AM, McHutchison J, Rice CM (2002) Hepatology 35:224

    Article  Google Scholar 

  44. Kolykhalov AA, Mihalik K, Feinstone SM, Rice CJ (2000) Virology 74:2046

    Article  CAS  Google Scholar 

  45. Lamarre D, Anderson PC, Bailey M, Beaulieu P, Bolger G, Bonneau P, Bös M, Cameron DR, Cartier M, Cordingley MG, Faucher A-M, Goudreau N, Kawai SH, Kukolj G, Lagacé L, LaPlante SR, Narjes H, Poupart M-A, Rancourt J, Sentjens RE, St George R, Simoneau B, Stelnmann G, Thibeault D, Tsantrizos YS, Weldon SM, Yong C-L, Linas-Brunet M (2003) Nature 426:186

    Article  CAS  Google Scholar 

  46. Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens RE, Calleja JL, Forns X, Erhardt A, Crönlein J, Chaves R, Yong C-L, Nehmiz G, Steinmann G (2004) Gasteroenterology 127:1347 (Doi:10 1016/j gastro 2004 08 002)

    Article  CAS  Google Scholar 

  47. Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T, Hostomska Z (1996) Cell 87:331

    Article  CAS  Google Scholar 

  48. Kim JL, Morgenstern KA, Lin C, Fox T, Dwyer MD, Landro JA, Chambers SP, Markland W, Lepre CA, O'Malley ET, Harbeson SL, Rice CM, Murcko MA, Caron PR, Thomson JA (1996) Cell 87:343

    Article  CAS  Google Scholar 

  49. Kakiuchi N, Hijikata M, Komoda Y, Tanji Y, Hirowatari Y, Shimotohno K (1995) Biochem Biophys Res Comm 210:1059

    Article  CAS  Google Scholar 

  50. Llinàs-Brunet M, Bailey M, Fazal G, Goulet S, Halmos T, LaPlante S, Maurice R, Poirier M, Poupart M-A, Thibeault D, Wernic D, Lamarre D (1998) Bioorganic and Medicinal Chemistry Letters 8:1713

    Article  Google Scholar 

  51. Steinkühler C, Biasiol G, Brunetti M, Urbani A, Koch U, Cortese R, Pessi A, De Francesco R (1998) Biochemistry 37:8899

    Article  Google Scholar 

  52. Llinàs-Brunet M, Bailey M, Déziel R, Fazal G, Gorys V, Goulet S, Halmos T, Maurice R, Poirier M, Poupart M-A, Rancourt J, Thibeault D, Wernic D, Lamarre D (1998) Bioorg Med Chem Lett 8:2719

    Article  Google Scholar 

  53. Bailey M, Halmos T, Goudreau N, Lescop E, Llinàs-Brunet M (2004) J Med Chem 47:3788

    Article  CAS  Google Scholar 

  54. LaPlante SR, Cameron DR, Aubry N, Lefebvre S, Kukolj G, Maurice R, Thibeault D, Lamarre D, Llinàs-Brunet M (1999) J Biol Chem 274:18618

    Article  CAS  Google Scholar 

  55. Llinàs-Brunet M, Bailey M, Fazal G, Ghiro E, Gorys V, Goulet S, Halmos T, Maurice R, Poirier M, Poupart M-A, Rancourt J, Thibeault D, Wernic D, Lamarre D (2000) Bioorg Med Chem Lett 10:2267

    Article  Google Scholar 

  56. LaPlante SR, Aubry N, Bonneau P, Kukolj G, Lamarre D, Lefebvre S, Li H, Llinàs-Brunet M, Plouffe C, Cameron D R (2000) Bioorg Med Chem Lett 10:2271

    Article  CAS  Google Scholar 

  57. Tsantrizos Y, Bolger G, Bonneau P, Cameron DR, Goudreau N, Kukolj G, LaPlante SR, Llinàs-Brunet M, Nar H, Lamarre D (2003) Angew Chem Int Ed 42:1356

    Article  CAS  Google Scholar 

  58. LaPlante SR, Aubry N, Deziel R, Ni F, Xu P (2000) J Am Chem Soc 122:12530

    Article  CAS  Google Scholar 

  59. Rancourt J, Cameron DR, Gorys V, Lamarre D, Poirier M, Thibeault D, Llinàs-Brunet M (2004) J Med Chem 47:2511

    Article  CAS  Google Scholar 

  60. Poupart M-A, Cameron DR, Chabot C, Ghiro E, Goudreau N, Goulet S, Poirier M, Tsantrizos Y (2001) J Org Chem 66:4743

    Article  CAS  Google Scholar 

  61. Goudreau N, Cameron DR, Bonneau P, Gorys V, Plouffe C, Poirier M, Lamarre D, Llinàs-Brunet M (2004) J Med Chem 47:123

    Article  CAS  Google Scholar 

  62. Llinàs-Brunet M, Bailey M, Ghiro E, Gorys V, Halmos T, Poirier M, Rancourt J, Goudreau N (2004) J Med Chem 47:6584

    Article  CAS  Google Scholar 

  63. Goudreau N, Brochu C, Cameron DR, Duceppe J-S, Faucher A-M, Ferland J-M, Grand-Maitre C, Poirier M, Simoneau B, Tsantrizos YS (2004) J Org Chem 69:6185

    Article  CAS  Google Scholar 

  64. Pause A, Kukolj G, Bailey M, Brault M, Do F, Halmos T, Lagace L, Maurice R, Marquis M, McKercher G, Pellerin C, Pilote L, Thibeault D, Lamarre D (2003) J Biol Chem 278:20374

    Article  CAS  Google Scholar 

  65. Ali S, Pellerin C, Lamarre D, Kukolj G (2004) J Virol 78:491

    Article  CAS  Google Scholar 

  66. Llinàs-Brunet M, Bailey M, Bolger G, Brochu C, Faucher AM, Ferland J-M, Garneau M, Ghiro E, Gorys V, Grand-Maitre C, Halmos T, Lapayre-Pachette N, Liard F, Poirier M, Rheame M, Tsantrizos YS, Lamarre D (2004) J Med Chem 47:1605

    Article  CAS  Google Scholar 

  67. Thibeault D, Bousquet C, Gingras R, Lagace L, Maurice R, White P, Lamarre D (2004) J Virol 78:7352

    Article  CAS  Google Scholar 

  68. Faucher A-M, Bailey M, Beaulieu PL, Brochu C, Duceppe J-S, Ferland J-M, Ghiro E, Gorys V, Halmos T, Kawai SH, Poirier M, Simoneau B, Tsantrizos YS, Llinàs-Brunet M (2004) Organic Letters 6:2901

    Article  CAS  Google Scholar 

  69. Kessler H, Bats JW, Griesinger C, Koll S, Will M, Wagner K (1988) J Am Chem Soc 110:1033

    Article  CAS  Google Scholar 

  70. Dellwo MJ, Wand JJ (1989) J Am Chem Soc 111:4571

    Article  CAS  Google Scholar 

  71. Palmer AG, Rance M, Wright P (1991) J Am Chem Soc 113:4371

    Article  CAS  Google Scholar 

  72. Detlefsen DJ, Hill SE, Day SH, Lee MS (1999) Curr Med Chem 6:353

    CAS  Google Scholar 

  73. Briand J, Kopple KJ (1995) J Biol NMR 6:347

    CAS  Google Scholar 

  74. Peng JW, Schiffer CA, Xu P, Gunsteren WF, Ernst RR (1996) J Bio NMR 8:453

    Article  CAS  Google Scholar 

  75. Zhu L, Prendergast FG, Kemple MD (1998) J Biol NMR 12:133

    Google Scholar 

  76. Friedrichs MS, Stouch TR, Bruccoleri RE, Mueller L, Constantine KL (1995) J Am Chem Soc 117:10855

    Article  CAS  Google Scholar 

  77. Ramirez-Alvarado M, Daragen VA, Serrano L, Mayo KH (1998) Protein Sci 7:720

    Article  CAS  Google Scholar 

  78. Daragen VA, Ilyina EE, Fields GB, Mayo KH (1997) Protein Sci 6:355

    Article  Google Scholar 

  79. Abragam A (1961) The Principles of Nuclear Magnetism. Clarendon Press, Oxford

    Google Scholar 

  80. Ernst RR, Bodenhausen G, Wokaun A (1987) Principles of Nuclear Magnetic Resonance in One and Two Dimensions. Clarendon Press, Oxford, pp 49–57

    Google Scholar 

  81. Levy GC, Lichter RL, Nelson GL (1980) Carbon-13 Nuclear Magnetic Resonance. 2nd edn., Chap. 8. Wiley, New York

    Google Scholar 

  82. Peng JW, Wagner G (1992) J Magn Reson 98:308

    CAS  Google Scholar 

  83. Peng JW, Wagner G (1992) Biochemistry 31:8571

    Article  CAS  Google Scholar 

  84. Lipari G, Szabo A (1982) J Am Chem Soc 104:4546

    Article  CAS  Google Scholar 

  85. Fersht A (1985) Enzyme Structure and Mechanisms. 2nd edn. Freeman and Co, New York

    Google Scholar 

  86. Polgár L (ed) (1989) Mechanisms of Protease Action. Chap. 3. CRC Press Inc, Boca Raton, FL

    Google Scholar 

  87. Hedstrom L (2002) Chem Rev 102:4501

    Article  CAS  Google Scholar 

  88. Barbato G, Cicero DO, Nardi MC, Steinkühler C, Cortese R, De Francesco R, Bazzo R (1999) J Mol Biol 289:371

    Article  CAS  Google Scholar 

  89. Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T, Margosiak S, Dagostino E, Hostomaska Z (1998) Clinical and Diagnostic Virology 10:151

    Article  CAS  Google Scholar 

  90. McCoy MA, Senior MM, Gesell JJ, Ramanathan L, Wyss DF (2001) J Mol Biol 305:1099

    Article  CAS  Google Scholar 

  91. Bianchi E, Pessi A (2002) Biopolymers 66:101

    Article  CAS  Google Scholar 

  92. Barbato G, Cicero DO, Cordier F, Narjes F, Gerlach B, Sambucini S, Grzesiek S, Matassa VG, De Francesco R, Bazzo R (2000) EMBO J 19:1195

    Article  CAS  Google Scholar 

  93. Urbani A, Bazzo R, Nardi MC, Cicero DO, De Francesco R, Steinkühler C, Barbato G (1998) J Biol Chem 273:18760

    Article  CAS  Google Scholar 

  94. Bianchi E, Orrù S, Dal Piaz F, Ingenito R, Casbarra A, Biasiol G, Koch U, Pucci P, Pessi A (1999) Biochemistry 38:13844

    Article  CAS  Google Scholar 

  95. Archer SJ, Camac DM, Wu ZJ, Farrow NA, Domaille PJ, Wasserman ZR, Bukhtiyarova M, Rizzo C, Jagannathan S, Mersinger LJ, Kettner CA (2002) Chem Biol 9:79

    Article  CAS  Google Scholar 

  96. Yan Y, Li Y, Munshi S, Sardana V, Cole JL, Sardana M, Steinkühler C, Tomei L, De Francesco R, Kuo L, Chen Z (1998) Protein Sci 7:837

    Article  CAS  Google Scholar 

  97. Trozzi C, Bartholomew L, Ceccacci A, Biasiol G, Pacini L, Altamura S, Narjes F, Muraglia E, Paonessa G, Koch U, De Francesco R, Steinkühler C, Migliaccio G (2003) J Virology 77:3669

    Article  CAS  Google Scholar 

  98. Lin C, Lin K, Luong Y-P, Rao RB, Wei Y-Y, Brennan DL, Fulghum JR, Hsiao H-M, Ma S, Maxwell JP, Cottrell KM, Perni RB, Gates CA, Kwong AD (2004) J Biol Chem 279:17508

    Article  CAS  Google Scholar 

  99. Tong L, Wengler G, Rossman MG (1993) J Mol Biol 230:228

    Article  CAS  Google Scholar 

  100. Tong L (2002) Chem Rev 102:4609

    Article  CAS  Google Scholar 

  101. LaPlante SR, Jakalian A, Aubry N, Bousquet Y, Ferland J-M, Gillard J, Lefebvre S, Poirier M, Tsantrizos YS, Kukolj G, Beaulieu PL (2004) Angew Chem Int Ed 43:4306

    Article  CAS  Google Scholar 

  102. Peng JW (2003) J Am Chem Soc 125:1116 MKW

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work described herein involved many colleagues at Boehringer Ingelheim, and I would like to acknowledge their valuable contributions. I am also grateful to M. Bös, R. Bethell, and M. Cordingley for their encouragement and support. I also thank N. Aubry, S. Kawai, J. Gillard, P. White, and P. Bonneau for insightful discussions or for critical reading of the manuscript.

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  1. Department of Chemistry, Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard St., Laval, H7S 2G5, Quebec, Canada

    Steven R. LaPlante

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Correspondence to Steven R. LaPlante .

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LaPlante, S.R. (2006). Exploiting Ligand and Receptor Adaptability in Rational Drug Design Using Dynamics and Structure-Based Strategies. In: Peters, T. (eds) Bioactive Conformation I. Topics in Current Chemistry, vol 272. Springer, Berlin, Heidelberg . https://doi.org/10.1007/128_2006_087

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