[Project supported by FrenchBIC] Nader Balbali: Characterization of peptidyl copper complexes as laccase and LPMO mimics by electrochemical methods
Nader BALBALI, from the METHROX team at the CPCV lab, Paris, spent one week in the ALAMBIC team at LCC in Toulouse. This project was supported by a grant from FrenchBIC.
My PhD project aims to develop peptidyl copper complexes mimicking enzymes activity to trigger selective release of drugs in vivo. In order to develop those complexes, peptidyl complexes combinatorial libraries have been prepared and specific laccase-activity screening assays have been established. Using the screening assays results, the best complexes were singled out, identified, synthetized on a larger scale and their activity was studied first in vitro and then, when suited, on a cellular model. Copper complexes characterization is a key factor to understand the catalytic mechanism at play, and more importantly to inspire the design of more efficient complexes via the synthesis of new peptidyl sequences impacting the geometry, coordination and redox properties of the Cu center and therefore the resulting catalytic activity of the cu complexes.
Thanks to a grant from FrenchBIC, a collaboration with Dr. Charlène Esmieu and Dr. Christelle Hureau from the ALAMBIC team at the Laboratoire de Chimie de Coordination, Toulouse (LCC, CNRS) was set in order to perform an in-depth characterization of these complexes.
During the week I spent in Toulouse, two complexes mimicking laccase-type activity were investigated by cyclic voltammetry and electron paramagnetic resonance spectroscopy giving us insightful information about their redox properties, their geometry and their coordination sphere. Additionally, the thermodynamic stability constants of these complexes were studied by UV-visible absorption and fluorescence titration through successive additions of copper as well as through competition with other ligands with known affinity constants. These results provided us useful preliminary data that will enable the in-depth characterization of the copper complexes and will help me to refine my research. These data will be introduced in an ANR grant proposal that will be submitted if it reaches the second step enabling further collaboration between our teams.
I would like to thank the FrenchBIC for the grant as well as Dr. Charlène Esmieu, Dr. Christelle Hureau and their team for hosting me. I spent a very instructive, fruitful and pleasant time within their team.