Plasmepsin inhibitors: Design, synthesis, inhibitory studies and crystal structure analysis

Journal of Peptide Research

Volumn 66, Issue 4, 2005, Pages 211-219

  Kesavulu, M M ^a   Gowda, A S Prakasha ^a   Ramya, T N C ^a   Surolia, N ^a   Suguna, K ^a  

^a INDIAN INSTITUTE OF SCIENCE   (India)

Author keywords

Aspartic protease; Malaria; Plasmepsin inhibition; Plasmepsins; Plasmodium falciparum

Indexed keywords

4 NITROBENZOYLLEUCINE BETA ALANINE; 4 NITROBENZOYLLEUCINE ISONIPECOTIC ACID; ASPARTIC PROTEINASE; BETA ALANINE; HEMOGLOBIN; ISONIPECOTIC ACID; PLASMEPSIN I; PLASMEPSIN INHIBITOR; UNCLASSIFIED DRUG;

ANALYTIC METHOD; ARTICLE; CRYSTAL STRUCTURE; CRYSTALLIZATION; DRUG DESIGN; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; MALARIA; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; STRUCTURE ANALYSIS;

ANIMALS; ASPARTIC ENDOPEPTIDASES; BETA-ALANINE; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; ISONIPECOTIC ACIDS; MAGNETIC RESONANCE SPECTROSCOPY; PLASMODIUM FALCIPARUM; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY;

PLASMODIUM FALCIPARUM;

EID: 25144452288     PISSN: 1397002X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1399-3011.2005.00288.x     Document Type: Article

References (25)

1. Breman, J.G., Alilio, M.S. & Mills, A. (2004) Conquering the intolerable burden of malaria: what's new, what's needed: a summary. Am. J. Trop. Med. Hyg. 71S, 1-15.
2. Oaks, S.C., Mitchell, V.S., Jr, Pearson, G.W. & Carpenter, C.C.J., eds (1991) Malaria: Obstacles and Opportunities. A report of the committee for the study on malaria prevention and control: Status review and alternate strategies. Division of International Health, Institute of Medicine, National Academy, Washington, DC.
3. White, N.J. (1998) Drug resistance in malaria. Br. Med. Bull. 54, 703-715.
4. Jiang, S., Prigge, S.T., Wei, L., Gao, Y.E., Hudson, T.H, Gerena, L., Dame, J.B. & Kyle, D.E. (2001) New class of small nonpeptidyl compounds blocks Plasmodium falciparum development in vitro by inhibiting plasmepsins. Antimicrob. Agents Chemother. 45, 2577-2584.
5. Rosenthal, P.J., McKerrow, J.H., Aikawa, M., Nagasawa, H. & Leech, J.H. (1988) A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum. J. Clin. Invest. 82, 1560-1566.
6. Eggleson, K.K., Duffin, K.L. & Goldberg, D.E. (1999) Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. J. Biol. Chem. 274, 32411-32417.
7. Francis, S.E., Gluzman, I.Y., Oksman, A., Knickerbocker, A., Mueller, R., Bryant, M., Sherman, D.R., Russell, D.G. & Goldberg, D.E. (1994) Molecular characterization and inhibition of Plasmodium falciparum aspartic hemogloinase. EMBO J. 13, 306-317.
8. Berry, C., Humphreys, J., Matharu, P., Granger, R., Horrocks, P., Moon, R.P., Certa, U., Ridley, R.G., Bur, D. & Kay, J. (1999) A distinct member of the aspartic proteinase gene family from the human malaria parasite Plasmodium falciparum. FEBS Lett. 447, 149-154.
9. Banerjee, R., Liu, J., Beatty, W., Klemba, M. & Goldberg, D.E. (2002) Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active site histidine. Proc. Natl. Acad. Sci. USA 99, 990-995.
10. Coombs, G.H., Goldberg, D.E., Klemba, M., Berry, C., Kay, J. & Mottram, J.C. (2001) Aspartic proteases of Plasmodium falciparam and other parasitic protozoa as drug targets. Trends Parasitol. 17, 532-537.
11. Noteberg, D., Hamelink, E., Hulten, J., Wahlgren, M., Vrang, L., Samuelsson, B. & Hallberg, A. (2003) Design and synthesis of plasmepsin I and plasmepsin II inhibitors with activity in Plasmodium falciparum-infected cultured human erythrocytes. J. Med. Chem. 46, 734-746.
12. Johansson, P.-O., Lindberg, J., Blackman, M.J., Kvarnstrom, I., Vrang, L., Hamelink, E., Hallberg, A., Rosenquist, A. & Samuelsson, B. (2005) 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. 48, 4400-4409.
13. Asojo, O.A., Gulnik, S.V., Afonina, E., Yu, B., Ellman, J.A., Haque, T.S. & Silva, A.M. (2003) Novel uncomplexed and complxed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum. J. Mol. Biol. 327, 173-181.
14. Mueller, R., Huerzeler, M. & Boss, C. (2003) Synthesis of Plasmepsin II inhibitors-Potential Antimalarial agents. Molecules 8, 556-564.
15. Asojo, O.A., Afonina, E., Gulnik, S.V., Yu, B., Erickson, J.W., Randad, R., Medjahed, D. & Silva, A.M. (2002) Structures of Ser205 mutant plasmepsin II from Plasmodium falciparum at 1.8 Å in complex with the inhibitors rs367 and rs3yo. Acta. cryst. D58, 2001-2008.
16. Dahlgren, A., Kvarnstrom, I., Vrang, L., Hamelink, E., Hallberg, A., Rosenquist & Samuelsson, A.B. (2003) New inhibitors of the malaria aspartyl proteases plasmepsin I and II. Bioorg. Med. Chem. 11, 3423-3437.
17. Ersmark, K., Feierberg, L, Bjelic, S., Hamelink, E., Hackett, F., Blackman, M.J., Hulten, J., Samuelsson, B., Aqvist, J. & Hallberg, A. (2004) Potent inhibitors of the Plasmodium falciparum enzymes plasmepsins I and II devoid of cathepsin D inhibitory activity. J. Med. Chem. 47, 110-122.
18. Silva, A.M., Lee, A.Y., Gulnik, S.V., Majer, P., Collins, J., Bhat, T.N., Collins, P.J., Cachau, R.E., Luker, K.E., Gluzman, I.Y., Francis, S.E., Oksman, A., Goldberg, D.E. & Erickson, J.W. (1996) Structure and inhibition of plasmepsin II, a hemoglobin degrading enzyme from Plasmodium falciparum. Proc. Natl. Acad. Sci. USA. 93, 10034-10039.
19. Prade, L., Jones, A.F., Boss, C., Richard-Bildstein, S., Meyer, S., Binkert, C. & Bur, D. (2005) X-ray structure of plasmepsin II complexed with a potent achiral inhibitor. J. Biol. Chem. 280, 23837-23843.
20. Trager, W. & Jenson, J.B. (1976) Human malaria parasites in continuous culture. Science 193, 673-675.
21. Lambros, C. & Vanderberg, J. (1979) Synchronization of Plasmodium falciparum erythrocytic stages in culture. J. Parasitol. 65, 418-420.
22. Ancelin, M.L., Calas, M., Bompart, J., Cordina, G., Martin, D., Ben Bari, M., Jei, T., Druilhe, P. & Vial, H.J. (1998) Antimalarial activity of 77 phospholipid polar head analogs: close correlation between inhibition of phospholipid metabolism and in vitro Plasmodium falciparum growth. Blood 91, 1426-1437.
23. Sheldrick, G.M. (1997) SHELXS 97, Program for Automatic Solution of Crystal Structures & SHELXL 97, Program for crystal structure refinement. University of Gottingen, Gottingen, Germany.
24. Tripos Associates, Inc. (1999) Program SYBYL. Tripos Associates, Inc., St Louis, MO.
25. Morris, G.M., Goodshell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K. & Olson, A.J. (1998) Automated docking using a Lamarckian genetic algorithm and empirical binding free energy function. J. Comp. Chem. 19, 1639-1662.