Article (Scientific journals)
Novel peptide inhibiting both TEM-1 beta-lactamase and penicillin-binding proteins.
Phichith, Denis; Bun, Sylvie; Padiolleau-Lefevre, Severine et al.
2010In FEBS Journal, 277 (23), p. 4965-72
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Keywords :
Antibodies, Catalytic/chemistry/genetics; Bacteriophage M13/genetics; Catalytic Domain; Kinetics; Models, Molecular; Mutagenesis; Penicillin-Binding Proteins/antagonists & inhibitors; Peptide Library; Peptides, Cyclic/chemistry/genetics/pharmacology; Peptidomimetics/chemistry/pharmacology; Protein Engineering; Tryptophan/chemistry; beta-Lactamase Inhibitors
Abstract :
[en] 9G4H9, a catalytic antibody displaying beta-lactamase-like activity, has been developed by the anti-idiotypic approach using beta-lactamase as the first antigen. Thus 9G4H9 represents the 'internal image' of beta-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 beta-lactamase (K(i) = 333 mum) and several penicillin-binding proteins (IC(5)(0) values ranging from 6-62 mum). 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 beta-lactamase.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Phichith, Denis
Bun, Sylvie
Padiolleau-Lefevre, Severine
Guellier, Adeline
Banh, Soun
Galleni, Moreno ;  Université de Liège - ULiège
Frère, Jean-Marie ;  Université de Liège > Département des sciences de la vie > Centre d'ingénierie des protéines
Thomas, Daniel
Friboulet, Alain
Avalle, Berangere
Language :
English
Title :
Novel peptide inhibiting both TEM-1 beta-lactamase and penicillin-binding proteins.
Publication date :
2010
Journal title :
FEBS Journal
ISSN :
1742-464X
eISSN :
1742-4658
Publisher :
Blackwell, Oxford, United Kingdom
Volume :
277
Issue :
23
Pages :
4965-72
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2010 The Authors Journal compilation (c) 2010 FEBS.
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since 27 November 2015

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