Novel peptide inhibiting both TEM-1 β-lactamase and penicillin-binding proteins.
9G4H9, a catalytic antibody displaying β-lactamase-like activity, has been developed by the anti-idiotypic approach using β-lactamase as the first antigen. Thus 9G4H9 represents the 'internal image' of β-lactamase. We selected a cyclic peptide anchored to a bacteriophage M13 library using 9G4H9 as the target. Pep90 is a cyclic heptapeptide enclosed between two cysteine residues. We showed that Pep90 could inhibit both TEM-1 β-lactamase (K(i)  = 333 μm) and several penicillin-binding proteins (IC₅₀ values ranging from 6-62 μm). We determined that the tryptophan residue of Pep90 is of crucial importance for its inhibitory activity. Using Pep90 as a scaffold, we generated a new class of peptidomimetics that retained inhibitory activity towards TEM-1 β-lactamase.
Université de Technologie de Compiègne - CNRS, UMR 6022, Génie Enzymatique et Cellulaire, Compiègne Cedex, France.
Denis
D
Phichith
Sylvie
S
Bun
Severine
S
Padiolleau-Lefevre
Adeline
A
Guellier
Soun
S
Banh
Moreno
M
Galleni
Jean-Marie
JM
Frere
Daniel
D
Thomas
Alain
A
Friboulet
Berangere
B
Avalle
D017151:Antibodies, Catalytic / Q000737:chemistry / Q000235:genetics; D017104:Bacteriophage M13 / Q000235:genetics; D020134:Catalytic Domain; D007700:Kinetics; D008958:Models, Molecular; D016296:Mutagenesis; D046915:Penicillin-Binding Proteins / Q000037:antagonists & inhibitors*; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology; D015202:Protein Engineering; D014364:Tryptophan / Q000737:chemistry; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases
D017151:Antibodies, Catalytic; D046915:Penicillin-Binding Proteins; D019151:Peptide Library; D010456:Peptides, Cyclic; D057786:Peptidomimetics; D065093:beta-Lactamase Inhibitors; D014364:Tryptophan; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1