Transition state mimetics of the plasmodium export element are potent inhibitors of plasmepsin v from P. falciparum and P. Vivax

Journal of Medicinal Chemistry

Volumn 57, Issue 18, 2014, Pages 7644-7662

  Sleebs, Brad E ^a,b   Gazdik, Michelle ^a,b   O'Neill, Matthew T ^a,b   Rajasekaran, Pravin ^a,b   Lopaticki, Sash ^a,b   Lackovic, Kurt ^a,b   Lowes, Kym ^a,b   Smith, Brian J ^c   Cowman, Alan F ^a,b   Boddey, Justin A ^a,b  

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c LA TROBE UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; CHLOROQUINE; PLASMEPSIN INHIBITOR; PLASMEPSIN V INHIBITOR; UNCLASSIFIED DRUG; ASPARTIC PROTEINASE; BIOMIMETIC MATERIAL; PLASMEPSIN; PROTEINASE INHIBITOR;

AMINO ACID SEQUENCE; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SYNTHESIS; ERYTHROCYTE; HUMAN; HUMAN CELL; IN VITRO STUDY; MOLECULAR MODEL; NONHUMAN; PARASITE VIABILITY; PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PROTEIN CLEAVAGE; PROTEIN TRANSPORT; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; ENZYMOLOGY; METABOLISM; PARASITOLOGY; PROTEIN CONFORMATION; PROTEIN DEGRADATION;

ASPARTIC ACID ENDOPEPTIDASES; BIOMIMETIC MATERIALS; CELL LINE; DRUG DISCOVERY; ERYTHROCYTES; HUMANS; MODELS, MOLECULAR; PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PROTEASE INHIBITORS; PROTEIN CONFORMATION; PROTEOLYSIS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84907459128     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500797g     Document Type: Article

References (45)

1. World Malaria Report; World Health Organization: Geneva, 2013; http://www.who.int/malaria/publications/world-malaria-report-2013/en/.
2. Mendis, K.; J, S. B.; P, M.; Carter, R. The neglected burden of Plasmodium vivax malaria Am. J. Trop. Med. Hyg. 2001, 64, 97-106
3. Marti, M.; Good, R. T.; Rug, M.; Knuepfer, E.; Cowman, A. F. Targeting malaria virulence and remodeling proteins to the host erythrocyte Science 2004, 306, 1930-1933
4. Hiller, N. L.; Bhattacharjee, S.; van Ooij, C.; Liolios, K.; Harrison, T.; Lopez-Estrano, C.; Haldar, K. A host-targeting signal in virulence proteins reveals a secretome in malarial infection Science 2004, 306, 1934-1937
5. Boddey, J. A.; Carvalho, T. G.; Hodder, A. N.; Sargeant, T. J.; Sleebs, B. E.; Marapana, D.; Lopaticki, S.; Nebl, T.; Cowman, A. F. Role of Plasmepsin V in export of diverse protein families in the Plasmodium falciparum exportome Traffic 2013, 14, 532-550
6. Sargeant, T. J.; Marti, M.; Caler, E.; Carlton, J. M.; Simpson, K.; Speed, T. P.; Cowman, A. F. Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites Genome Biol. 2006, 7, R12
7. Maier, A. G.; Rug, M.; O'Neill, M. T.; Brown, M.; Chakravorty, S.; Szestak, T.; Chesson, J.; Wu, Y.; Hughes, K.; Coppel, R. L.; Newbold, C.; Beeson, J. G.; Craig, A.; Crabb, B. S.; Cowman, A. F. Exported proteins required for virulence and rigidity of Plasmodium falciparum -infected human erythrocytes Cell 2008, 134, 48-61
8. Chang, H. H.; Falick, A. M.; Carlton, P. M.; Sedat, J. W.; DeRisi, J. L.; Marletta, M. A. N-Terminal processing of proteins exported by malaria parasites Mol. Biochem. Parasitol. 2008, 160, 107-115
9. Boddey, J. A.; Moritz, R. L.; Simpson, R. J.; Cowman, A. F. Role of the Plasmodium export element in trafficking parasite proteins to the infected erythrocyte Traffic 2009, 10, 285-299
10. Russo, I.; Babbitt, S.; Muralidharan, V.; Butler, T.; Oksman, A.; Goldberg, D. E. Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte Nature 2010, 463, 632-636
11. Sleebs, B. E.; Lopaticki, S.; Marapana, D. S.; O'Neil, M.; Rajasekaran, P.; Gazdik, M.; Günther, S.; Whitehead, L. W.; Lowes, K. N.; Barfod, L.; Hviid, L.; Shaw, P. J.; Hodder, A. N.; Smith, B. J.; Cowman, A. F.; Boddey, J. A. Inhibition of plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display and survival of malaria parasites PLoS Biol. 2014, 12, e1001897
12. Akinyi, S.; Hanssen, E.; Meyer, E. V. S.; Jiang, J.; Korir, C. C.; Singh, B.; Lapp, S.; Barnwell, J. W.; Tilley, L.; Galinski, M. R. A 95 kDa protein of Plasmodium vivax and P. cynomolgi visualized by three-dimensional tomography in the caveola-vesicle complexes (Schüffner's dots) of infected erythrocytes is a member of the PHIST family Mol. Microbiol. 2012, 84, 816-831
13. Boddey, J. A.; Hodder, A. N.; Gunther, S.; Gilson, P. R.; Patsiouras, H.; Kapp, E. A.; Pearce, J. A.; de Koning-Ward, T. F.; Simpson, R. J.; Crabb, B. S.; Cowman, A. F. An aspartyl protease directs malaria effector proteins to the host cell Nature 2010, 463, 627-631
14. Klemba, M.; Goldberg, D. E. Characterization of plasmepsin V, a membrane-bound aspartic protease homolog in the endoplasmic reticulum of Plasmodium falciparum Mol. Biochem. Parasitol. 2005, 143, 183-191
15. Kappe, S. H.; Vaughan, A. M.; Boddey, J. A.; Cowman, A. F. That was then but this is now: malaria research in the time of an eradication agenda Science 2010, 328, 862-866
16. Eisenstein, M. Drug development: Holding out for reinforcements Nature 2012, 484, S16-S18
17. Johansson, P.-O.; Chen, Y.; Belfrage, A. K.; Blackman, M. J.; Kvarnström, I.; Jansson, K.; Vrang, L.; Hamelink, E.; Hallberg, A.; Rosenquist, Å.; Samuelsson, B. Design and synthesis of potent inhibitors of the malaria aspartyl proteases plasmepsin I and II. Use of solid-phase synthesis to explore novel statine motifs J. Med. Chem. 2004, 47, 3353-3366
18. Johansson, P.-O.; Lindberg, J.; Blackman, M. J.; Kvarnström, I.; Vrang, L.; Hamelink, E.; Hallberg, A.; Rosenquist, Å.; Samuelsson, B. Design and synthesis of potent inhibitors of plasmepsin I and II: X-ray crystal structure of inhibitor in complex with plasmepsin II J. Med. Chem. 2005, 48, 4400-4409
19. Nöteberg, D.; Hamelink, E.; Hultén, J.; Wahlgren, M.; Vrang, L.; Samuelsson, B.; Hallberg, A. Design and synthesis of plasmepsin I and plasmepsin II inhibitors with activity in Plasmodium falciparum -infected cultured human erythrocytes J. Med. Chem. 2003, 46, 734-746
20. Nöteberg, D.; Schaal, W.; Hamelink, E.; Vrang, L.; Larhed, M. High-speed optimization of inhibitors of the malarial proteases plasmepsin I and II J. Comb. Chem. 2003, 5, 456-464
21. Bonilla, J. A.; Bonilla, T. D.; Yowell, C. A.; Fujioka, H.; Dame, J. B. Critical roles for the digestive vacuole plasmepsins of Plasmodium falciparum in vacuolar function Mol. Microbiol. 2007, 65, 64-75
22. Eder, J.; Hommel, U.; Cumin, F.; Martoglio, B.; Gerhartz, B. Aspartic proteases in drug disocvery Curr. Pharm. Des. 2007, 13, 271-285
23. Abbenante, G.; Fairlie, D. P. Protease inhibitors in the clinic Med. Chem. 2005, 1, 71-104
24. Drag, M.; Salvesen, G. S. Emerging principles in protease-based drug discovery Nature Rev. Drug Discovery 2010, 9, 690-701
25. Eder, J.; Hommel, U.; Cumin, F.; Martoglio, B.; Gerhartz, B. Aspartic proteases in drug disocvery Curr. Pharm. Des. 2007, 13, 271-285
26. Baxter, E. W.; Conway, K. A.; Kennis, L.; Bischoff, F.; Mercken, M. H.; De Winter, H. L.; Reynolds, C. H.; Tounge, B. A.; Luo, C.; Scott, M. K.; Huang, Y.; Braeken, M.; Pieters, S. M. A.; Berthelot, D. J. C.; Masure, S.; Bruinzeel, W. D.; Jordan, A. D.; Parker, M. H.; Boyd, R. E.; Qu, J.; Alexander, R. S.; Brenneman, D. E.; Reitz, A. B. 2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta-site APP cleaving enzyme): use of structure based design to convert a micromolar hit into a nanomolar lead J. Med. Chem. 2007, 50, 4261-4264
27. Malamas, M. S.; Barnes, K.; Johnson, M.; Hui, Y.; Zhou, P.; Turner, J.; Hu, Y.; Wagner, E.; Fan, K.; Chopra, R.; Olland, A.; Bard, J.; Pangalos, M.; Reinhart, P.; Robichaud, A. J. Di-substituted pyridinyl aminohydantoins as potent and highly selective human beta-secretase (BACE1) inhibitors Bioorg. Med. Chem. 2010, 18, 630-639
28. Porcari, V.; Magnoni, L.; Terstappen, G. C.; Fecke, W. A continuous time-resolved fluorescence assay for identification of BACE1 inhibitors Assay Drug Dev. Technol. 2005, 3, 287-297
29. Yasuda, Y.; Kageyama, T.; Akamine, A.; Shibata, M.; Kominami, E.; Uchiyama, Y.; Yamamoto, K. Characterization of new fluorogenic substrates for the rapid and sensitive assay of cathepsin E and cathepsin D J. Biochem. 1999, 125, 1137-1143
30. Straub, A.; Roehrig, S.; Hillisch, A. Oral, direct thrombin and factor Xa inhibitors: the replacement for warfarin, leeches, and pig intestines? Angew. Chem., Int. Ed. 2011, 50, 4574-4590
31. Rawlings, N. D.; Barrett, A. J.; Bateman, A. MEROPS: the database of proteolytic enzymes, their substrates and inhibitors Nucleic Acids Res. 2012, 40, D343-D350
32. Mastan, B. S.; Kumari, A.; Gupta, D.; Mishra, S.; Kumar, K. A. Gene disruption reveals a dispensable role for plasmepsin VII in the Plasmodium berghei life cycle Mol. Biochem. Parasitol. 2014, 195, 10-13
33. Coombs, G. H.; Goldberg, D. E.; Klemba, M.; Berry, C.; Kay, J.; Mottram, J. C. Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets Trends Parasitol. 2001, 17, 532-537
34. Šali, A.; Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints J. Mol. Biol. 1993, 234, 779-815
35. Prade, L.; Jones, A. F.; Boss, C.; Richard-Bildstein, S.; Meyer, S.; Binkert, C.; Bur, D. X-ray structure of plasmepsin II complexed with a potent achiral inhibitor J. Biol. Chem. 2005, 280, 23837-23843
36. Bernstein, N. K.; Cherney, M. M.; Yowell, C. A.; Dame, J. B.; James, M. N. Structural insights into the activation of P. vivax plasmepsin J. Mol. Biol. 2003, 329, 505-524
37. Clarke, B.; Demont, E.; Dingwall, C.; Dunsdon, R.; Faller, A.; Hawkins, J.; Hussain, I.; MacPherson, D.; Maile, G.; Matico, R.; Milner, P.; Mosley, J.; Naylor, A.; O'Brien, A.; Redshaw, S.; Riddell, D.; Rowland, P.; Soleil, V.; Smith, K. J.; Stanway, S.; Stemp, G.; Sweitzer, S.; Theobald, P.; Vesey, D.; Walter, D. S.; Ward, J.; Wayne, G. BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character Bioorg. Med. Chem. Lett. 2008, 18, 1017-1021
38. Behnen, J.; Koster, H.; Neudert, G.; Craan, T.; Heine, A.; Klebe, G. Experimental and computational active site mapping as as starting point to fragment-based lead discovery ChemMedChem 2012, 7, 248-261
39. Hess, B.; Kutzner, C.; van der Spool, D.; Lindahl, E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation J. Chem. Theory Comput. 2008, 4, 435-437
40. Jorgensen, W. L.; Tirado-Rives, J. The OPLS force filed for proteins. Energy minimizations for crystals of cyclic peptides and crambin J. Am. Chem. Soc. 1998, 110, 1657-1666
41. Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling J. Chem. Phys. 2007, 126, 014101
42. Essman, U.; Perela, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A smooth particle mesh Ewald method J. Chem. Phys. 1995, 103, 8577-92
43. Hess, B. P-LINCS: a parallel linear constraint solver for molecular simulation J. Chem. Theory Comput. 2008, 4, 116-122
44. Gamo, F.-J.; Sanz, L. M.; Vidal, J.; de Cozar, C.; Alvarez, E.; Lavandera, J.-L.; Vanderwall, D. E.; Green, D. V. S.; Kumar, V.; Hasan, S.; Brown, J. R.; Peishoff, C. E.; Cardon, L. R.; Garcia-Bustos, J. F. Thousands of chemical starting points for antimalarial lead identification Nature 2010, 465, 305-310
45. Calculator Plugins were used for structure property prediction and calculation, Marvin 14.7.7.0, 2014, ChemAxon (http://www.chemaxon.com).