Le Roux P, Blanot D, Mengin-Lecreulx D, Van Heijenoort J
Laboratory of Bacterial Envelopes and Peptides, CNRS URA 1131, University of Paris-South, Orsay, France.
Int J Pept Protein Res. 1991 Feb;37(2):103-11.
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(Cl)-ambo-Apm and ambo-Apm-L-Ala(Cl). In the two latter cases, Apm was associated with antibacterial amino acid beta-chloro-L-alanine [L-Ala(Cl)], an inhibitor of alanine racemase and transaminase B. The peptides displayed weak or no antibacterial activities; nevertheless, those containing L-Ala(Cl) 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(Cl)-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.
利用肽转运策略，我们设计并合成了几种含有2-氨基庚二酸（Apm）的新肽，Apm是细菌中二氨基庚二酸途径的抑制剂：L-赖氨酸-ambo-Apm、ambo-Apm-L-赖氨酸、L-赖氨酸-L-丙氨酸-ambo-Apm、ambo-Apm-L-丙氨酸-L-赖氨酸、L-丙氨酸（Cl）-ambo-Apm和ambo-Apm-L-丙氨酸（Cl）。在后两种情况下，Apm与抗菌氨基酸β-氯-L-丙氨酸[L-丙氨酸（Cl）]结合，L-丙氨酸（Cl）是丙氨酸消旋酶和转氨酶B的抑制剂。这些肽显示出较弱的抗菌活性或无抗菌活性；然而，那些含有L-丙氨酸（Cl）的肽在存在恢复蛋白质合成的氨基酸时具有较低的最低抑菌浓度（MIC）值。当在基本培养基中生长的指数期大肠杆菌细胞上进行测试时，这些肽没有作用或具有抑菌作用，但当生长培养基补充特定氨基酸时，可以观察到重要的溶菌作用，特别是对于含L-丙氨酸（Cl）的肽。结果表明，含L-赖氨酸的肽的微弱或无作用是由于摄取不良所致。
