Synthetic tripeptides as alternate substrates of murein peptide ligase (Mpl).
Biochimie
; 95(6): 1120-6, 2013 Jun.
Article
in En
| MEDLINE
| ID: mdl-23270797
ABSTRACT
Murein peptide ligase (Mpl) is an enzyme found in Gram-negative bacteria. It catalyses the addition of tripeptide L-Ala-γ-D-Glu-meso-diaminopimelate to nucleotide precursor UDP-N-acetylmuramic acid during the recycling of peptidoglycan. Although not essential, this enzyme represents an interesting target for antibacterial compounds through the synthesis of alternate substrates whose incorporation into peptidoglycan might be deleterious for the bacterial cell. Therefore, we have synthesised 10 tripeptides L-Ala-γ-D-Glu-Xaa in which Xaa represents amino acids different from diaminopimelic acid. Tripeptide with Xaa = ε-D-Lys proved to be an excellent substrate of Escherichia coli Mpl in vitro. Tripeptides with Xaa = p-amino- or p-nitro-L-phenylalanine were poor substrates, while tripeptides with Xaa = D- or L-2-aminopimelate, DL-2-aminoheptanoic acid, L-Glu, L-norleucine, L-norvaline, L-2-aminobutyric acid or L-Ala were not substrates at all. Although a good Mpl substrate, the D-Lys-containing tripeptide was devoid of antibacterial activity against E. coli, presumably owing to poor uptake.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Peptide Synthases
/
Escherichia coli Proteins
Language:
En
Journal:
Biochimie
Year:
2013
Document type:
Article
Affiliation country:
France