Université de Strasbourg

Peptides shuttles

Peptides as biological shuttles for copper ions

USIAS Fellows : Peter Faller et Christelle Hureau

Biological membranes play an absolute key role in life, as they form the border between inside and outside and hence control what enters and what leaves a cell. Cells need a tight control of the concentration of all chemicals (like proteins, metabolites, ions etc.). Loss of controls about the concentration of the entities can lead to disease and ultimately to death.

Copper is an essential metal ion and is important as a catalytic center is several processes including very fundamental ones like energy production. That's why loss of control over Cu is very dangerous and is well documented by two genetic diseases, called Wilson's and Menkes' diseases, one leading to an accumulation of Cu and the other one to a lack of Cu. Both diseases are lethal at young ages if not treated. Also in several neurodegenerative diseases, a Cu dyshomeostasis seems to be involved. In Alzheimer's disease, small molecules having a so called Cu-ionophore activity (able to transport Cu through membranes) showed promising results in therapeutic approaches.

The project consists of designing and investigating peptidic platforms to bind, transfer and deliver copper ions intra-cellularly. pH or redox changes are exploited as stimuli for intracellular Cu release. Peptides have been chosen for their high modularity and their multi-functional ability. The proposed approach is based on the coupling of a cell penetrating moiety and a copper binding sequence. The project aims to provide fundamental insights about this new type of copper transport, to obtain a new tool to probe the importance of copper homeostasis in biological processes and might be of interest for therapeutic applications.

 

Investissements d'Avenir