1887

Abstract

Analogues of di- and tripeptides in which the peptide backbone is modified have been examined for antibacterial activity and for uptake into Aminoxy and hydrazino types, in which the peptide linkage is replaced, respectively, by -CO-NHO- or -CO-NH-NH-, were active against and retro, α-aza, tetrazole, and hydroxamic types were inactive. Highest potency against all three species was found in aminoxy analogues containing -2-aminoxypropionic acid (-OAla) residues, Ala--OAla being active at < 1 mg 1. Uptake into was seen with all active types, but, with the exception of hydroxamic analogues, not with the inactive types. Following uptake the toxic analogues were rapidly hydrolysed and the constituent amino acid residues underwent exodus. The substrate specificities of the peptide transport systems have been further defined on the basis of our results.

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/content/journal/micro/10.1099/00221287-129-12-3701
1983-12-01
2024-05-03
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References

  1. Allen J. G., Atherton F. R., Hall M. J., Hassall C. H., Holmes S. W., Lambert R. W., Nisbet L. J., Ringrose P. S. 1978; Phosphonopeptides, a new class of synthetic antibacterial agents. Nature; London: 27256–58
    [Google Scholar]
  2. Alves R. A., Payne J. W. 1980; The number and nature of the peptide-transport systems of Escherichia coli: characterization of specific transport mutants. Biochemical Society Transactions 8:704–705
    [Google Scholar]
  3. Atherton F. R., Hall M. J., Hassall C. H., Lambert R. W., Lloyd W. J., Ringrose P. S. 1979; Phosphonopeptides as antibacterial agents: mechanism of action of alaphosphin. Antimicrobial Agents and Chemotherapy 15:696–705
    [Google Scholar]
  4. Atherton F. R., Hall M. J., Hassall C. H., Holmes S. W., Lambert R. W., Lloyd W. J., Ringrose P. S. 1980; Phosphonopeptide antibacterial agents related to alafosfalin: design, synthesis, and structure-activity relationships. Antimicrobial Agents and Chemotherapy 18:897–905
    [Google Scholar]
  5. Barak Z., Gilvarg C. 1975; Specialized peptide transport system in Escherichia coli. Journal of Bacteriology 122:1200–1207
    [Google Scholar]
  6. Briggs M. T., Morley J. S. 1979; Aminoxy-analogues of aspartame and gastrin C-terminal tetra-peptide amide. Journal of the Chemical Society, Perkin I2138–2143
    [Google Scholar]
  7. Davis B. D., Mingioli E. S. 1950; Mutants of Escherichia coli requiring methionine or vitamin B12. Journal of Bacteriology 60:17–28
    [Google Scholar]
  8. John R. A., Charteris A., Fowler L. J. 1978; The reaction of amino-oxyacetate with pyridoxal phosphate-dependent enzymes. Biochemical Journal 171:771–779
    [Google Scholar]
  9. Miller C. G., Schwartz G. 1978; Peptidase-deficient mutants of Escherichia coli. Journal of Bacteriology 135:603–611
    [Google Scholar]
  10. Morley J. S. 1968; Structure-activity relationships. Federation Proceedings 27:1314–1317
    [Google Scholar]
  11. Morley J. S. 1980; Modulation of the action of regulatory peptides by structural modification. Trends in Pharmacological Sciences 1:463–468
    [Google Scholar]
  12. Morley J. S. 1981; Nomenclature. Neuropeptides 1:231–235
    [Google Scholar]
  13. Naider F., Becker J. M. 1975; Multiplicity of oligopeptide transport systems in Escherichia coli. Journal of Bacteriology 122:1208–1215
    [Google Scholar]
  14. Neuhaus F. C., Hammes W. P. 1981; Inhibition of cell wall biosynthesis by analogues of alanine. Pharmacology and Therapeutics 14:265–319
    [Google Scholar]
  15. Payne J. W. 1968; Oligopeptide transport in Escherichia coli: specificity with respect to side chain and distinction from dipeptide transport. Journal of Biological Chemistry 243:3395–3403
    [Google Scholar]
  16. Payne J. W. 1977; Transport and hydrolysis of peptides by microorganisms. In Peptide Transport and Hydrolysis (Ciba Foundation Symposia 50 pp. 305–334 Amsterdam:: Associated Scientific Publishers.;
    [Google Scholar]
  17. Payne J. W. 1980; Transport and utilisation of peptides by bacteria. In Microorganisms and Nitrogen Sources pp. 211–256 Payne J. W. Edited by Chichester & New York:: John Wiley.;
    [Google Scholar]
  18. Payne J. W., Bell G. 1979; Direct determination of the properties of peptide transport systems in Escherichia coli using a fluorescent-labeling procedure. Journal of Bacteriology 137:447–455
    [Google Scholar]
  19. Payne J. W., Nisbet T. M. 1981; Continuous monitoring of substrate uptake by microorganisms using fluorescamine: application to peptide transport by Saccharomyces cerevisiae and Streptococcus faecalis. Journal of Applied Biochemistry 3:447–458
    [Google Scholar]
  20. Ringrose P. S. 1980; Peptides as antimicrobial agents. In Microorganisms and Nitrogen Sources pp. 641–692 Payne J. W. Edited by Chichester & New York:: John Wiley.;
    [Google Scholar]
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