PL EN


Preferences help
enabled [disable] Abstract
Number of results
2000 | 47 | 1 | 113-120
Article title

Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro.

Content
Title variants
Languages of publication
EN
Abstracts
EN
Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds differed in the precise mode of action. The inhibitory effect of I on the activity of the eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the binding site of eEF-2 on the ribosome was blocked by this compound. eEF-2 has been identified as the primary target of II and eEF-1 as the primary target of DAPI in the system studied.
Publisher

Year
Volume
47
Issue
1
Pages
113-120
Physical description
Dates
published
2000
received
1999-10-25
Contributors
  • Department of Medicinal Chemistry and Drug Technology, Medical Academy of Białystok, 15-230 Białystok 8, Poland
author
  • Department of General and Organic Chemistry, Institute of Chemistry, Medical Academy of Białystok, 15-230 Białystok 8, Poland
  • Department of Medicinal Chemistry and Drug Technology, Medical Academy of Białystok, 15-230 Białystok 8, Poland
  • Department of General and Organic Chemistry, Institute of Chemistry, Medical Academy of Białystok, 15-230 Białystok 8, Poland
References
  • 1. Schoenbach, E.B. & Greenspan, E.M. (1948) The pharmacology, mode of action and therapeutic potentialities of stilbamidine, pentamidine, propamidine and other aromatic diamidines a review. Medicine 27, 327-377.
  • 2. Blagburn, B.L., Sunderman, C.A., Lindsay, D.S., Hall, J.E. & Tidwell, R.R. (1991) Inhibition of Cryptosporidium parvum in neonatal Hsd:(ICR)BR Swiss mice by polyether ionophores and aromatic amidines. Antimicrob. Agents Chemother. 35, 1520-1523.
  • 3. Bell, C.A., Hall, E.D., Kyle, E., Grogl, M., Ohemeng, K.A., Allen, M.A. & Tidwell, R.R. (1990) Structure-activity relationships of analogs of pentamidine against Plasmodium falciparvum and Leishmania mexicana amazonensis. Antimicrob. Agents Chemother. 34, 1381-1386.
  • 4. Wispelwey, B. & Pearson, R.D. (1991) Pentamidine: A review. Infect. Control Hosp. Epidemiol. 12, 375-381.
  • 5. Gazzard, B.G. (1989) Pneumocystis carinii pneumonia and its treatment in patients with AIDS. J. Antimicrob. Chemother. 23, 67-75.
  • 6. Cory, M., Tidwell, R.R. & Fairley, T.A. (1992) Structure and DNA binding activity of analogues of 1,5-bis(4-amidinophenoxy)pentane (pentamidine). J. Med. Chem. 35, 431-438.
  • 7. Shapiro, T.A. & Englund, P.T. (1990) Selective cleavage of kinetoplast DNA minicircles promoted by antityrypanosomal drugs. Proc. Natl. Acad. Sci. U.S.A. 87, 950-954.
  • 8. Zimmer, C. & Wähnert, U. (1986) Non-intercalating DNA-binding ligands: Specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material. Prog. Biophys. Mol. Biol. 47, 31-112.
  • 9. Luck, G., Zimmer, C. & Schweizer, D. (1988) DNA binding studies of the nonintercalative ligand pentamidine: dA dT base-pair preference. Stud. Biophys. 125, 107-119.
  • 10. Fox, K.R., Sansom, C.E. & Stevens, M.F.G. (1990) Footprinting studies on the sequence-selective binding of pentamidine to DNA. FEBS Lett. 266, 150-154.
  • 11. Lowe, P.R., Sansom, C.E., Schwalbe, C.H. & Stevens, M.F.G. (1989) Crystal structure and molecular modelling of the antimicrobial drug pentamidine. J. Chem. Soc., Chem. Commun. 1164-1165.
  • 12. Sansom, C.E., Laughton, C.A., Neidle, S., Schwalbe, C.H. & Stevens, M.F.G. (1990) Structural studies on bioactive compounds. XIV. Molecular modelling of the interactions between pentamidine and DNA. Anti-Cancer Drug Design 5, 243-248.
  • 13. Kopka, M.L., Yoon, C., Goodsell, D., Pjura, P. & Dickerson, R.E. (1985) Binding of an antitumour drug to DNA netropsin and CGCGAATTBrCGCG. J. Mol. Biol. 183, 553-563.
  • 14. Neidle, S. (1997) Crystallographic insights into DNA minor groove recognition by drugs. Biopolymers 44, 105-121.
  • 15. Moldave, K. (1985) Eukaryotic protein synthesis. Annu. Rev. Biochem. 54, 1109-1149.
  • 16. Gałasiński, W. & Moldave, K. (1969) Purification of aminoacyltransferase II (translocation factor) from rat liver. J. Biol. Chem. 244, 6527-6532.
  • 17. Jabłonowska, K., Kopacz-Jodczyk, T., Niedźwiecka, J. & Gałasiński, W. (1983) Isolation and characterization of elongation factor EF-2 from Guerin tumour. Acta Biochim. Polon. 30, 381-388.
  • 18. Gajko, A., Gałasiński, W. & Gindzieński, A. (1994) Multiformity of elongation factor eEF-2 isolated from rat liver cells. Biochem. Biophys. Res. Commun. 202, 844-849.
  • 19. Fairley, T.A., Tidwell, R.R., Donkor, A., Naiman, N.A., Ohemeng, K.A., Bentley, J.A. & Cory, M. (1993) Structure, DNA minor groove binding and base pair specificity of alkyl- and aryl-linked bis(amidinobenzimidazoles) and bis(amidinoindoles). J. Med. Chem. 36, 1746-1753.
  • 20. Proud, C.G. (1994) Peptide-chain elongation in eukaryotes. Mol. Biol. Rep. 19, 161-170.
  • 21. Rug, B., Rattan, I.S., Clark, B.F.C. & Merrick, W.C. (1990) Eukaryotic protein elongation factors. Trends Biochem. Sci. 15, 420-424.
  • 22. Nierhaus, K.H. (1996) An elongation factor turn-on. Nature 379, 491-492.
  • 23. Rodnina, M.V., Savelsbergh, A., Katunin, V. & Wintermeyer, W. (1997) Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome. Nature 385, 37-41.
  • 24. Perenthesis, J.P., Phan, L.W., Gleason, H., LaPorte, D.C, Livingston, D.M. & Bodley, J.W. (1992) Saccharomyces cerevisiae elongation factor 2. Genetic cloning, characterization of expression and G-domain modeling. J. Biol. Chem. 267, 1190-1197.
  • 25. Nilsson, L. & Nygard, O. (1985) Localization of the sites of ADP-ribosylation and GTP binding in the eukaryotic elongation factor EF-2. Eur. J. Biochem. 148, 299-304.
  • 26. Nygard, O. & Nilsson, L. (1989) Characterization of the ribosomal properties required for formation of a GTPase active complex with the eukaryotic elongation factor 2. Eur. J. Biochem. 179, 603-608.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv47i1p113kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.