Peptides containing 2-aminopimelic acid

Synthesis and study of in vitro effects on bacterial cells*

Authors

  • PIERRE LE ROUX,

    1. Laboratory of Bacterial Envelopes and Peptides. CNRS URA 1131, University of Paris-South, Orsay, France
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  • DIDIER BLANOT,

    Corresponding author
    1. Laboratory of Bacterial Envelopes and Peptides. CNRS URA 1131, University of Paris-South, Orsay, France
      Address: Dr. Didier Blanot Laboratoire des Enveloppes Bactériennes et des Peptides URA 1131 duCNRS Bâtiment 432 Université de Paris-Sud 91405 Orsay France
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  • DOMINIQUE MENGIN-LECREULX,

    1. Laboratory of Bacterial Envelopes and Peptides. CNRS URA 1131, University of Paris-South, Orsay, France
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  • JEAN VAN HEIJENOORT

    1. Laboratory of Bacterial Envelopes and Peptides. CNRS URA 1131, University of Paris-South, Orsay, France
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  • *

    Part of this work has been presented at the 20th European Peptide Symposium (Tübingen, FRG, September 1988) (1). Abbreviations for amino acids, peptides, and their derivatives are those recommended by the IUPAC-IUB (European J. Biochem. 1984, 138, 9–37). In particular, the prefix ambo is used instead of the symbol DL in diastereoisomeric peptides whose ratio may not be unity.

Address: Dr. Didier Blanot Laboratoire des Enveloppes Bactériennes et des Peptides URA 1131 duCNRS Bâtiment 432 Université de Paris-Sud 91405 Orsay France

Abstract

Taking advantage of the peptide transport strategy, we have designed and synthesized several new peptides containing 2-aminopimelic acid (Apm), an inhibitor of the diaminopimelate pathway in bacteria: L-LYS-ambo-Apm, ambo-Apm-L-Lys, L-Lys-L-Ala-ambo-Apm, ambo-Apm-L-Ala-L-Lys, L-Ala(CI)-ambo-Apm and ambo-Apm-L-Ala(CI). In the two latter cases, Apm was associated with antibacterial amino acid β-chloro-L-alanine [L-Ala(CI)], an inhibitor of alanine racemase and transaminase B. The peptides displayed weak or no antibacterial activities; nevertheless, those containing L-Ala(CI) had low MIC values in the presence of amino acids restoring protein synthesis. When tested on exponential phase Escherichia coli cells grown in minimal medium, the peptides were without effect or bacteriostatic, but important bacteriolytic effects could be observed, especially for the L-Ala(CI)-containing peptides, when the growth medium was supplemented with specific amino acids. It was demonstrated that the weak or nil effect of the L-lysine-containing peptides was due to a poor uptake.

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