Biological Applications and Evolutionary Origins of Ionophores

  • Berton C. Pressman
  • Norberto T. deGuzman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 84)


The structure and physical chemical properties are reviewed of various ionophores, small molecules which transport cations across biological membranes. The subclass of carboxylic ionophores has dramatic pharmacological properties, dilating the coronary arteries and increasing cardiac contractility, which make them especially interesting. They share related structures containing a terminal carboxyl group hydrogen bonded to the opposite end of the molecule in a cyclic conformation. A variety of oxygen atoms, in heterocyclic rings or linear ether configurations, hydroxyls, and/or ketonic carbonyls as well as carboxyls, focus upon a sphere which can ligand to appropriately fitting cations via ion-dipole interaction. Extreme dependency of liganding energy on fit confers striking ion selectivity upon ionophores. It is speculated that carboxylic ionophores originated as prosthetic groups of ion carriers and represent a natural experiment by the streptomyces genus in the construction of non-proteinaceous binding sites. Ultimately production of these prosthetic groups hypertrophied and subsequently they were elaborated as antibiotics to provide their producers with a survival advantage over competitors. Analogous ionophores have now been synthesized. Unique applications for these compounds are emerging, based either on their selective toxicity or ability to modify physiological processes by altering membrane gradients.


Cardiac Contractility Heterocyclic Ring Streptomyces Genus Liganding Oxygen Neutral Ionophore 
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  1. 1.
    MOORE, C. and PRESSMAN, B.C.: Biochem. Biophys. Res. Commun. 15 (1964) 562.CrossRefGoogle Scholar
  2. 2.
    PRESSMAN, B. C.: Proc. Natl. Acad. Sci. U.S.A. 53 (1965) 1076.PubMedCrossRefGoogle Scholar
  3. 3.
    OVCHINNIKOV, YU., IVANOV, V. T. and SHKROB, A. M. : Membrane Active Complexones, B.B.A. Library, Vol. 12, Elsevier, New York, (1974).Google Scholar
  4. 4.
    PRESSMAN, B. C.: Am. Rev. Biochem. 45 (1976) 501.CrossRefGoogle Scholar
  5. 5.
    PRESSMAN, B. C.: Ion transport induction by valinomycin and related antibiotics, Wirkungsmechanismen von Fungiziden and Antibiotics. Academie-Verlag. Berlin. (1967) p. 3.Google Scholar
  6. 6.
    PRESSMAN, B.C.: Carboxylic ionophores as mobile carriers for divalent ions. The Role of Membranes in Metabolic Regulation (Mehlman, M. A., Hanson, R.W., Eds.) Academic. New York (1972) p. 149.Google Scholar
  7. 7.
    PRESSMAN, B. C.: Fed. Proc. 32 (1973) 1698.PubMedGoogle Scholar
  8. 8.
    REED, P. W. and LARDY, H. A.: Antiobiotic A23187 as a probe for the study of calcium and magnesium function in biological systems, The Role of Membranes in Metabolic Regulation (Mehlman, M. A., Hanson, R. W. Eds.) Academic. New York (1972) p. 111.Google Scholar
  9. 9.
    PRESSMAN, B. C. and DEGUZMAN, N. T.: Ann. N. Y. Acad. Sci. 264 (1975) 373.PubMedCrossRefGoogle Scholar
  10. 10.
    DEGUZMAN, N. T. and PRESSMAN, B. C.: Circulation 49 (1974) 1072.Google Scholar
  11. 11.
    CASWELL, A. H. and PRESSMAN, B. C.: Biochem. Biophys. Res. Commun. 49 (1972) 292.PubMedCrossRefGoogle Scholar
  12. 12.
    DEGANI, H., FRIEDMAN, H.L., NAVON, G. and KOSSOWER, E. M.: J. Chem. Soc. Chem. Commun. 49 (1973) 431.CrossRefGoogle Scholar
  13. 13.
    PRESSMAN, B. C. and DEGUZMAN, N. T.: Ann. N. Y. Acad. Sci. 227 (1974) 380.PubMedCrossRefGoogle Scholar
  14. 14.
    PFEIFFER, D. R., REED, P. W. and LARDY, H. A.: Biochemistry 19 (1974) 4007.CrossRefGoogle Scholar
  15. 15.
    HELGESON, R. C., KOGA, K., TIMKO, J. M. and CRAM, D. J.: J. Am. Chem. Soc. 95 (1973) 3021.CrossRefGoogle Scholar
  16. 16.
    CRAM, D. J.: Synthetic host-guest chemistry, Applications of Biochemical Systems in Organic Chemistry (Jones, J. B., Ed.) Wiley. Interscience New York (1976).Google Scholar
  17. 17.
    WIELAND, T., FAULSTICH, H., BURGERMEISTER, W., OTTING, W., SHEMYAKIN, M. M., OVCHINNIKOV, YU. A., and MALENKOY, G.G.: FEBS Lett. 9 (1970) 89.PubMedCrossRefGoogle Scholar
  18. 18.
    CHAO, Y. and CRAM, D. J.: J. Am. Chem. Soc. 98 (1976) 1015.CrossRefGoogle Scholar
  19. 19.
    KANNE, R. and ZAHNER, H.: Z. Naturforsch. 31 (1976) 115.Google Scholar
  20. 20.
    SHUMARD, R. F. and COLLENDER, M.E.: Antimicrobial Agents and Chemotherapy — 1967 (1968) 369.Google Scholar
  21. 21.
    RAUN, A. P., COOLEY, C. O., POTTER, E. L., RICHARDSON, L. F., RATHMACHER, R. P. and KENNEDY, R. W. : J. Anim. Sci. 39 (1974) 250.Google Scholar
  22. 22.
    SAGAWA, T., HIRANO, S., TAKAHASHI, H., TANAKA, N., OISHI, H., ANDO, K., and TOGASHI, K.: J. Econ. Entomol. 65 (1972) 372.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Berton C. Pressman
    • 1
  • Norberto T. deGuzman
    • 1
  1. 1.Department of Pharmacology, School of MedicineUniversity of MiamiMiamiUSA

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