Cyclic peptides bearing a side-chain tail: A tool to model the structure and reactivity of protein zinc sites.

Olivier Sénèque (1) , Emilie Bourlès (1) , Vincent Lebrun (1) , Estelle Bonnet (1) , Pascal Dumy (2) , Jean-Marc Latour (1)

1 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
2 DCM - Département de Chimie Moléculaire

A new peptide design has been introduced to model the tetracysteinate zinc sites involving CXXC motifs present in beta-hairpins. It is based on a cyclic peptide incorporating one CXXC motif in addition to a variable CXC motif in a linear chain grafted onto the cycle via a glutamate or a lysine side chain. This 20-amino acid design has been used to model the Zn(Cys)4 sites of the heat shock protein Hsp33. TheZn2+ and Co2+ complexes were characterized by UV/vis, CD and NMR spectroscopy. The structures of two metallated peptides were solved by NMR. An excellent similarly was achieved between the model peptide and the target protein, both at the metal binding site and in the surrounding hydrogen bond network. Preliminary reactivity studies toward H2O2 are reported and show that the best model fit the kinetics observed for Hsp33.

Mots clés: bioinorganic chemistry; cysteines; NMR spectroscopy; peptides; zinc

Domaines: Chimie de coordination

Olivier Sénèque, Emilie Bourlès, Vincent Lebrun, Estelle Bonnet, Pascal Dumy, et al.. Cyclic peptides bearing a side-chain tail: A tool to model the structure and reactivity of protein zinc sites.. Angewandte Chemie International Edition, 2008, 47 (36), pp.6888-6891. ⟨10.1002/anie.200800677⟩. ⟨hal-00373744⟩