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Molecular Aspects of Chemotherapy pp 127–142Cite as

Exploitation of Peptide Transport Systems in the Design of Antimicrobial Agents

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Abstract

The occurrence of transport systems for the uptake of peptide nutrients is widespread amongst bacteria and fungi. In general, two or three such systems occur, the overlapping and complementary specificities of which ensure the efficient uptake of all peptides comprising 2–5 residues. The broad structural specificities of these systems also permit uptake of modified natural peptides and varied peptide analogues. This situation is being exploited in the synthesis of peptide smugglins, i.e. compounds in which a normally impermeant moiety is incorporated into a peptide so that it can be actively accumulated; once inside the organism, the impermeant moiety can be released enzymically but will be unable to efflux. In this way, potentially toxic compounds can be directed against normally inaccessible, intracellular targets. Various natural, antibacterial peptide smugglins are known to exist.

Here we describe novel assays, using purified peptide binding proteins, to characterise substrate binding, the results of which can be used in the design of optimal peptide carriers for uptake of smugglins. In addition, we report on the use in vitro of antibacterial smugglins together with different antimicrobial agents that offer interesting prospects for combinative drug therapy.

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Author information

Authors and Affiliations

  1. School of Biological Sciences, University of Wales, Bangor, Gwynedd, LL57 2UW, UK

    D. R. Tyreman, M. W. Smith, G. M. Payne & J. W. Payne

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  1. D. R. Tyreman
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  2. M. W. Smith
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  3. G. M. Payne
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  4. J. W. Payne
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Editor information

Editors and Affiliations

  1. Polish Academy of Sciences, University of Warsaw, Warsaw, Poland

    David Shugar

  2. Institute of Biochemistry & Biophysics, Polish Academy of Science, 36 Rakowiecka St., 02-532, Warszawa, Poland

    David Shugar

  3. Department of Biophysics, Institute of Experimental Physics, University of Warsaw, 93 Żwirki i Wigury St., 02-089, Warszawa, Poland

    David Shugar

  4. Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteura St., 02-093, Warszawa, Poland

    Wojciech Rode

  5. Department of Pharmaceutical Technology & Biochemistry, Technical University of Gdańsk, 80-952, Gdańsk, Poland

    Edward Borowski

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© 1992 Springer-Verlag Berlin Heidelberg

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Tyreman, D.R., Smith, M.W., Payne, G.M., Payne, J.W. (1992). Exploitation of Peptide Transport Systems in the Design of Antimicrobial Agents. In: Shugar, D., Rode, W., Borowski, E. (eds) Molecular Aspects of Chemotherapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-02740-0_8

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  • DOI: https://doi.org/10.1007/978-3-662-02740-0_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-02742-4

  • Online ISBN: 978-3-662-02740-0

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