Novel peptide inhibiting both TEM-1 β-lactamase and penicillin-binding proteins

Denis Phichith (1) , Sylvie Bun (1) , Severine Padiolleau-Lefevre (1) , Adeline Guellier (1) , Soun Banh (1) , Moreno Galleni (2) , Jean‐marie Frere (2) , Daniel Thomas (1) , Alain Friboulet (1) , Berangere Avalle (1)

1 GEC - Génie Enzymatique et Cellulaire
2 Université de Liège

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 (Ki = 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.

Mots clés: class; A β-lactamase TEM-1; inhibition; penicillin-binding proteins; peptide; peptidomimetic

Domaines: Chimie

Denis Phichith, Sylvie Bun, Severine Padiolleau-Lefevre, Adeline Guellier, Soun Banh, et al.. Novel peptide inhibiting both TEM-1 β-lactamase and penicillin-binding proteins. FEBS Journal, 2010, 277 (23), pp.4965-4972. ⟨10.1111/j.1742-4658.2010.07906.x⟩. ⟨hal-00535992⟩