Fragment-based screen against HIV protease

Chemical Biology and Drug Design

Volumn 75, Issue 3, 2010, Pages 257-268

  Perryman, Alexander L ^a   Zhang, Qing ^a,b   Soutter, Holly H ^a,c   Rosenfeld, Robin ^a,d   McRee, Duncan E ^d,e   Olson, Arthur J ^a   Elder, John E ^a   David Stout, C ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b GLAXOSMITHKLINE   (China)

^c PFIZER INC   (United States)

^d ActiveSight   (United States)

^e Sorrento Technologies   (United States)

Author keywords

Allosteric inhibitor; Crystal structure; Fragment screen; HIV protease; Multidrug resistance

Indexed keywords

ARGININE; GLUTAMINE; GLYCINE; LEUCINE; LYSINE; METHIONINE; PROLINE; PROTEINASE; TRYPTOPHAN; VALINE; BENZOTHIOPHENE; CARBOXYLIC ACID; CYCLOHEXANOL DERIVATIVE; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; RECOMBINANT PROTEIN; THIOPHENE DERIVATIVE;

ARTICLE; BINDING AFFINITY; BINDING SITE; ENZYME BINDING; ENZYME STRUCTURE; HYDROGEN BOND; PRIORITY JOURNAL; PROTEIN INTERACTION; X RAY CRYSTALLOGRAPHY; CHEMISTRY; ENZYME ACTIVE SITE; GENETICS; HUMAN; METABOLISM;

BINDING SITES; CARBOXYLIC ACIDS; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; CYCLOHEXANOLS; HIV PROTEASE; HIV PROTEASE INHIBITORS; HUMANS; HYDROGEN BONDING; RECOMBINANT PROTEINS; THIOPHENES;

EID: 76049105922     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2009.00943.x     Document Type: Article

References (59)

1. Little S.J., Holte S., Routy J.P., Daar E.S., Markowitz M., Collier A.C., Koup R.A., Mellors J.W., Connick E., Conway B., Kilby M., Wang L., Whitcomb J.M., Hellmann N.S., Richman D.D. (2002) Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med 347 : 385 394.
2. Ghosn J., Pellegrin I., Goujard C., Deveau C., Viard J.-P., Galimand J., Harzic M., Tamalet C., Meyer L., Rouzioux C., Chaix M.-L. (2006) HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time. AIDS 20 : 159 170.
3. Brenner B., Routy J.-P., Quan Y., Moisi D., Oliveira M., Turner D., Wainberg M.A. & co-investigators of the Quebec Primary Infection Study 2004) Persistence of multidrug-resistant HIV-1 in primary infection leading to superinfection. AIDS 18 : 1653 1660.
4. Ohtaka H., Freire E. (2005) Adaptive inhibitors of HIV-1 protease. Prog Biophys Mol Biol 88 : 193 208.
5. Heaslet H., Rosenfeld R., Giffin M., Lin Y.-C., Tam K., Torbett B.E., Elder J.E., McRee D.E., Stout C.D. (2007) Conformational flexibility in the flap domains of ligand free HIV protease. Acta Cryst D 63 : 866 875.
6. Freedberg D.I., Ishima R., Jacob J., Wang Y.-X., Kustanovich I., Louis J.M., Torchia D.A. (2002) Rapid structural fluctuations of the free HIV protease flaps in solution: relationship to crystal structures and comparison with predictions of dynamics calculations. Prot Sci 11 : 221 232.
7. Katoh E., Louis J.M., Yamazaki T., Gronenborn A.M., Torchia D.A., Ishima R. (2003) A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Prot. Sci. 12 : 1376 1385.
8. Galiano L., Bonora M., Fanucci G.A. (2007) Interflap Distances in HIV-1 Protease Determined by Pulsed EPR Measurements. J Am Chem Soc 129 : 11004 11005.
9. Ding F., Layten M., Simmerling C. (2008) Solution Structure of HIV-1 Protease Flaps Probed by Comparison of Molecular Dynamics Simulation Ensembles and EPR Experiments. J Am Chem Soc 130 : 7184 7185.
10. Torbeev V.Y., Raghuraman H., Mandal K., Senapati S., Perozo E., Kent S.B.H. (2009) Dynamics of "Flap" Structures in Three HIV-1 Protease/Inhibitor Complexes Probed by Total Chemical Synthesis and Pulse-EPR Spectroscopy. J Am Chem Soc 131 : 884 885.
11. Perryman A.L., Lin J.H., McCammon J.A. (2006) Restrained molecular dynamics simulations of HIV-1 protease: the first step in validating a new target for drug design. Biopolymers 82 : 272 284.
12. Tozzini V., McCammon J.A. (2005) A coarse grained model for the dynamics of flap opening in HIV-1 protease. Chem Phys Lett 413 : 123 128.
13. Scott W.R.P., Schiffer C.A. (2000) Curling of Flap Tips in HIV-1 Protease as a Mechanism for Substrate Entry and Tolerance of Drug Resistance. Structure 8 : 1259 1265.
14. Kurt N., Scott W.R.P., Schiffer C.A., Haliloglu T. (2003) Cooperative fluctuations of unliganded and substrate-bound HIV-1 protease: a structure-based analysis on a variety of conformations from crystallography and molecular dynamics simulations. Proteins 51 : 409 422.
15. Singh G., Senapati S. (2008) Molecular dynamics simulations of ligand-induced flap closing in HIV-1 protease approach X-ray resolution: establishing the role of bound water in the flap closing mechanism. Biochemistry 47 : 10657 10664.
16. Logsdon B.C., Vickrey J.F., Martin P., Proteasa G., Koepke J.I., Terlecky S.R., Wawrzak Z., Winters M.A., Merigan T.C., Kovari L.C. (2004) Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. J Virol 78 : 3123 3132.
17. Martin P., Vickrey J.F., Proteasa G., Jimenez Y.L., Wawrzak Z., Winters M.A., Merigan T.C., Kovari L.C. (2005) Wide Open 1.3 Å Structure of a Multi-drug Resistant HIV-1 Protease Represents a Novel Drug Target. Structure 13 : 1887 1895.
18. Liu F., Kovalevsky A.Y., Louis J.M., Boross P.I., Wang Y.F., Harrison R.W., Weber I.T. (2006) Mechanism of Drug Resistance Revealed by the Crystal Structure of the Unliganded HIV-1 Protease with F53L Mutation. J Mol Biol 358 : 1191 1199.
19. Galliano L., Ding F., Veloro A.M., Blackburn M.E., Simmerling C., Fanucci G.E. (2009) Drug Pressure Selected Mutations in HIV-1 Protease Alter Flap Conformations. J Am Chem Soc 131 : 430 431.
20. Reiling K.K., Endres N.F., Dauber D.S., Craik C.S., Stroud R.M. (2002) Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and the thermodynamic binding mode examined in a 1.09 Å structure. Biochem. 41 : 4582 4594.
21. Perryman A.L., Lin J.-H., McCammon J.A. (2004) HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: possible contributions to drug resistance and a potential new target site for drugs. Prot. Sci. 13 : 1108 1123.
22. Heaslet H.A., Kutilek V., Morris G.M., Lin Y.-C., Elder J.H., Torbett B.E., Stout C.D. (2006) Structural Insights into the Mechanisms of Drug Resistance in HIV-1 Protease NL4-3. J Mol Biol 356 : 967 981.
23. Luque I., Todd M.J., Gomez J., Semo N., Freire E. (1998) Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis. Biochem. 37 : 5791 5797.
24. Rees D.C., Congreve M., Murray C.W., Carr R. (2004) Fragment-based lead discovery. Nat Rev Drug Discov 3 : 660 672.
25. Erlanson D.A., McDowell R.S., O'Brien T. (2004) Fragment-based drug discovery. J Med Chem. 47 : 3463 3482.
26. Jhoti H. (2005) A new school for screening. Nat Biotechnol 23 : 184 186.
27. Hajduk P.J., Greer J. (2007) A decade of fragment-based drug design: strategic advances and lessons learned. Nat Rev Drug Discov 6 : 211 219.
28. Congreve M., Chessari G., Tisi D., Woodhead A.J. (2008) Recent Developments in Fragment-Based Drug Discovery. J Med Chem 51 : 3661 3680.
29. Bartoli S., Fincham C.I., Fattori D. (2007) Fragment-based drug design: combining philosophy with technology. Curr Opin Drug Discov Develop 10 : 422 429.
30. Carr R.A.E., Congreve M., Murray C.W., Rees D.C. (2005) Fragment-based lead discovery: leads by design. Drug Discov Today 10 : 987 992.
31. Hopkins A.L., Groom C.R., Alex A. (2004) Ligand efficiency: a useful metric for lead selection. Drug Discov Today 9 : 430 431.
32. Wunberg T., Hendrix M., Hillisch A., Lobell M., Meier H., Schmeck C., Wild H., Hinzen B. (2006) Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits. Drug Discov Today 11 : 175 180.
33. Kesaru G., Makara G.M. (2006) Hit discovery, hit-to-lead approaches. Drug Discov Today 11 : 741 748.
34. Beuscher A., Olson A.J., Goodsell D.S. (2005) Identifying protein binding sites and optimal ligands. Lett Drug Design Discov 2 : 255 259.
35. Harris R., Olson A.J., Goodsell D.S. (2008) Automated prediction of ligand-binding sites in proteins. Proteins 70 : 1506 1517.
36. Buhler B., Lin Y.C., Morris G., Olson A.J., Wong C.-H., Richman D.D., Elder J.H., Torbett B.E. (2001) Viral Evolution in Response to the Broad-Based Retroviral Protease Inhibitor TL-3. J Virol 75 : 9502 9508.
37. Pflugrath J.W. (1999) The finer things in X-ray diffraction data collection. Acta Cryst D 55 : 1718 1725.
38. Cohen A.E., Ellis P.J., Miller M.D., Deacon A.M., Phizackerley R.P. (2002) An automated system to mount cryo-cooled protein crystals on a synchrotron beamline, using compact sample cassettes and a small-scale robot. J Appl Cryst 35 : 720 726.
39. McPhillips T.M., McPhillips S.E., Chiu H.J., Cohen A.E., Deacon A.M., Ellis P.J., Garman E., Gonzalez A., Sauter N.K., Phizackerley R.P., Soltis S.M., Kuhn P. (2002) Blu-Ice and the distributed control system: software for data acquisition and instrument control at macromolecular crystallography beamlines. J Synchrotron Radiat 9 : 401 406.
40. González A., Moorhead P., McPhillips S.E., Song J., Sharp K., Taylor J.R., Adams P.D., Sauter N.K., Soltis S.M. (2007) Web-Ice: integrated data collection and analysis for macromolecular crystallography. J Appl Cryst 41 : 176 184.
41. Leslie A.G.W. (2006) The integration of macromolecular diffraction data. Acta Cryst D 62 : 48 57.
42. CCP4, Mosflm Collaborative Computational Project, Number 4 1994) The CCP4 suite: programs for protein crystallography. Acta Cryst D 50 : 760 763.
43. Murshudov G.N., Vagin A.A., Dodson E.J. (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Cryst D 53 : 240 255.
44. McRee D.E., Israel M. (2008) XtalView, protein structure solution and protein graphics, a short history. J Struct Biol 163 : 208 213.
45. Badger J., Rosenfeld R., McRee D.E. (2006) Active Sight fragment library 1 for lead discovery. San Diego, CA : Active Sight.
46. Soltis S.M., Cohen A.E., Deacon A., Eriksson T., González A., McPhillips S., Chui H. et al. (2008) New paradigm for macromolecular crystallography experiments at SSRL: automated crystal screening and remote data collection. Acta Cryst D 64 : 1210 1221.
47. Zhang Q., Heaslet H., Stout C.D., Olson A.J. (2008) MapDock: A Program for Automated Fitting of Fragments on Noisy X-ray Density Maps from Fragment Screening. San Diego, CA : Poster presentation at Fragment-Based Lead Discovery Conference p. 18 20.
48. Sanner M.F. (1999) Python: a programming language for software integration and development. J Mol Graph Model 17 : 57 61.
49. DeLano W.L., Lam J.W. (2005) PyMOL: a communications tool for computational models. Washington, DC : Abstracts of Papers, 230th ACS National Meeting Aug. 28-Sept. 1.
50. Damm K.L., Ung P.M., Quintero J.J., Gestwicki J.E., Carlson H.A. (2008) A poke in the eye: Inhibiting HIV-1 protease through its flap-recognition pocket. Biopolymers 89 : 643 652.
51. Böttcher J., Blum A., Dörr S., Heine A., Diederich W.E., Klebe G. (2008) Targeting the Open-Flap Conformation of HIV-1 Protease with Pyrrolidine-Based Inhibitors. ChemMedChem 3 : 1337 1344.
52. Warnke D., Barreto J., Zelalem T. (2007) Antiretroviral drugs. J. Clin Pharmacology 47 : 1570 1579.
53. Chellappan S., Kairys V., Fernandes M.X., Schiffer C., Gilson M.K. (2007) Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Proteins 68 : 561 567. (Pubitemid 46981948)
54. Ghosh A.K., Chapsal B.D., Weber I.T., Mitsuya H. (2008) Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. Acc Chem Res 41 : 78 86.
55. Cihlar T., He G.-X., Liu X., Chen J.M., Hatada M., Swaminathan S., McDermott M.J., Yang Z.-Y., Mulato A.S., Chen X., Leavitt S.A., Stray K.M., Lee W.A. (2006) Suppression of HIV-1 Protease Inhibitor Resistance by Phosphonate-mediated Solvent Anchoring. J Mol Biol 363 : 635 647.
56. Lee G.M., Craik C.S. (2009) Trapping Moving Targets with Small Molecules. Science 324 : 213 215.
57. Hornak V., Simmerling C. (2007) Targeting structural flexibility in HIV-1 protease inhibitor binding. Drug Discov Today 12 : 132 138.
58. Colman P.M. (2009) New Antivirals and Drug Resistance. Annu Rev Biochem 78 : 95 118.
59. Spinelli S., Leu Q.Z., Alzari P.M., Hirel P.H., Poljak R.J. (1991) The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie 73 : 1391 1396.