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Selective inhibitors of plasmepsin II of Plasmodium falciparum on the basis of pepstatin

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Abstract

A number of new inhibitors of plasmepsin II (PlmII) Plasmodium falciparum, which was one of the key factors of survival of malarial parasite, was synthesized. The inhibitors were analogues of pepstatin with different substitutions for the alanine residue. Effects of the inhibitors on human PlmII and cathepsin D were studied. Inhibition of PlmII by the substrate was found. This discovery required modification of the Henderson method for determination of inhibition constants. Two synthesized inhibitors were shown to exhibit a pronounced selectivity to PlmII (K i = 5.5 and 5 nM) in comparison with that of cathepsin D (K i = 230 and 3000 nM, respectively).

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Abbreviations

CatD:

cathepsin D

CS :

the H-Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe-OH chromogenic substrate

PlmII-PlmV:

plasmepsins II–V

Pst:

pepstatin

References

  1. Banerjee, R., Liu, J., Beatty, W., Pelosof, L., Klemba, M., and Goldberg, D.E., Proc. Natl. Acad. Sci. USA, 2002, vol. 99, pp. 990–995.

    Article  PubMed  CAS  Google Scholar 

  2. Coombs, G.H., Goldberg, D.E., Klemba, M., Berry, C., Kay, J., and Mottram, J.C., Trends in Parasitology, 2001, vol. 17, pp. 532–537.

    Article  PubMed  CAS  Google Scholar 

  3. Goldberg, D.E., Slater, A.F., Cerami, A., and Henderson, G.B., Proc. Natl. Acad. Sci. USA, 1990, vol. 87, pp. 2931–2935.

    Article  PubMed  CAS  Google Scholar 

  4. Goldberg, D.E., Slater, A.F., Beavis, R., Chait, B., Cerami, A., and Henderson, G.B., J. Exp. Med., 1991, vol. 173, pp. 961–969.

    Article  PubMed  CAS  Google Scholar 

  5. Glusman, I.Y., Francis, S.E., Oksman, A., Smith, C.E., Duffin, K.L., and Goldberg, D.E., J. Clin. Invest., 1994, vol. 93, pp. 1602–1608.

    Article  Google Scholar 

  6. Liu, J., Istvan, E.S., and Goldberg, D.E., J. Biol. Chem., 2006, vol. 281, pp. 38 682–38 688.

    CAS  Google Scholar 

  7. Prade, L., Jones, A.F., Boss, C., Richard-Bildstein, S., Meyer, S., Binkert, C., and Bur, D., J. Biol. Chem., 2005, vol. 280, pp. 23 837–23 843.

    Article  CAS  Google Scholar 

  8. Francis, S.E., Banerjee, R., and Goldberg, D.E., J. Biol. Chem., 1997, vol. 27, pp. 14 961–14 968.

    Google Scholar 

  9. Francis, S.E., Glusman, I.Y., Oksman, A., Knickerbocker, A., Mueller, R., Bryant, M.L., Sherman, D.R., Russel, D.G., and Goldberg, D.E., EMBO J., 1994, vol. 13, pp. 306–317.

    PubMed  CAS  Google Scholar 

  10. Hill, J., Tyas, L., Phylip, L.H., Kay, J., Dunn, B.M., and Berry, C., FEBS Lett., 1994, vol. 352, pp. 155–158.

    Article  PubMed  CAS  Google Scholar 

  11. Tyas, L., Gluzman, I., Moon, R.P., Rupp, K., Westling, J., Ridley, R.G., Kay, J., Goldberg, D.E., and Berry, C., FEBS Lett., 1999, vol. 454, pp. 210–214.

    Article  PubMed  CAS  Google Scholar 

  12. Silva, A.M., Lee, A.Y., Gulnik, S.V., Maier, P., Collins, J., Bhat, T.N., Collins, P.J., Cachau, R.E., Luker, K.E., Glusman, I.Y., Francis, S.E., Oksman, A., Goldberg, D.E., and Erickson, J.W., Proc. Natl. Acad. Sci. USA, 1996, vol. 99, pp. 990–995.

    Google Scholar 

  13. Westling, J., Cipullo, P., Hung, S.H., Saft, H., Dame, J.B., and Dunn, B.M., Protein Sci., 1999, vol. 8, pp. 2001–2009.

    Article  PubMed  CAS  Google Scholar 

  14. Tyas, L., Moon, R.P., Loetscher, H., Dunn, B.M., Kay, J., Ridley, R.G., and Berry, C., Adv. Exp. Med. Biol., 1998, vol. 436, pp. 407–411.

    PubMed  CAS  Google Scholar 

  15. Henderson, P.J.F., Biochem. J., 1972, vol. 127, pp. 321–333.

    PubMed  CAS  Google Scholar 

  16. Baldwin, E.T., Bhat, T.N., Gulnik, S., Hosur, M.V., Sowder, R.C., Cachau, R.E., Collins, J., Silva, A.M., and Erickson, J.W., Proc. Natl. Acad. Sci. USA, 1993, vol. 90, pp. 6796–6800.

    Article  PubMed  CAS  Google Scholar 

  17. Baldwin, J.E., Killin, S.J., Aldington, R.M., and Spiegel, U., Tetrahedron, 1988, vol. 44, p. 2633.

    Article  CAS  Google Scholar 

  18. Bodanszky, M., Martinez, J., Priestley, G.P., Gardner, J.D., and Mutt, V., J. Med. Chem., 1978, vol. 21, pp. 1030–1035.

    Article  PubMed  CAS  Google Scholar 

  19. Mauren, P.J. and Miller, M.J., J. Org. Chem., 1981, vol. 46, p. 2835.

    Article  Google Scholar 

  20. Organic Syntheses, Collective vol. 1, second ed. Translated under the title Sintezy organicheskikh preparatov, Kazansky, B.A., Ed., Moscow, 1944.

  21. Grobelny, D., Maslak, P., and Witek, S., Tetrahedron Lett., 1979, vol. 20, p. 2639.

    Article  Google Scholar 

  22. Gisin, B.F., Helv. Chim. Acta, 1973, vol. 56, pp. 1476–1482.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia

    L. D. Rumsh, A. G. Mikhailova, I. V. Mikhura, I. A. Prudchenko, L. D. Chikin, I. I. Mikhaleva, E. N. Kaliberda, N. I. Dergousova, E. E. Mel’nikov & A. A. Formanovskii

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  1. L. D. Rumsh
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  2. A. G. Mikhailova
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  3. I. V. Mikhura
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  4. I. A. Prudchenko
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  5. L. D. Chikin
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  6. I. I. Mikhaleva
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  7. E. N. Kaliberda
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  8. N. I. Dergousova
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  9. E. E. Mel’nikov
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  10. A. A. Formanovskii
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Correspondence to L. D. Rumsh.

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Original Russian Text © L.D. Rumsh, A.G. Mikhailova, I.V. Mikhura, I.A. Prudchenko, L.D. Chikin, I.I. Mikhaleva, E.N. Kaliberda, N.I. Dergousova, E.E. Mel’nikov, A.A. Formanovskii, 2008, published in Bioorganicheskaya Khimiya, 2008, Vol. 34, No. 6, pp. 739–746.

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Rumsh, L.D., Mikhailova, A.G., Mikhura, I.V. et al. Selective inhibitors of plasmepsin II of Plasmodium falciparum on the basis of pepstatin. Russ J Bioorg Chem 34, 660–667 (2008). https://doi.org/10.1134/S1068162008060034

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  • DOI: https://doi.org/10.1134/S1068162008060034

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