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Chem. Commun. [BCB/POMAM]

oct. 19 2018

Summary :

Peptides and proteins with N-terminal amino acid sequences NH2-Xxx-Zzz-His (XZH) form well established high affinity CuII-complexes. Key example is Asp-Ala-His in serum albumin, a Cu-transporter in the blood. This opens a straightforward way to add a high affinity CuII-binding site to almost any peptide or protein, by chemical or recombinant approaches. These motif has been used to equip peptides and proteins with a multitude of functions based on the redox activity of Cu, mostly oxidative cleavage of DNA, RNA, sugars, proteins etc. useful in anticancer or antimicrobial drugs. More recent research suggests novel biological functions, mainly based on the redox inertness of CuII bound to  this motif, like PET imaging, chelation therapies (for instance in Alzheimer’s disease and other types of neurodegeneration), antioxidant units, etc.

Hence, there seems to be a discrepancy. On the one handCu(II)–XZH is used to produce ROS, for which an efficient redox cycling of Cu is warranted, on the other hand, the XZH motif is used to redox silence Cu, based on an arrest of its redox cycling once Cu is bound to XZH. Hence the present work addresses this question, and shows that the redox activity this Cu(II–XZH complexes shows very low redox activity and hence are inefficient for oxidative cleavage of biomolecules.


The application of Cu(II)-Xxx-Zzz-His (ATCUN-peptides) as artificial metalloenzymes
is limited by their low catalytic-redox activity and disruption by Cu(I)-chelators.


Reference :

Alice Santoro, Gulshan Walke, Bertrand Vileno, Prasad P. Kulkarni, Laurent Raibaut and Peter Faller

Low catalytic activity of the Cu(II)-binding motif (Xxx-Zzz-His; ATCUN) in reactive oxygen species production and inhibition by the Cu(I)-chelator BCS

Chem. Commun., 2018, 54, 11945 - DOI : 10.1039/c8cc06040a

Contact chercheurs :

Alice Santoro et Peter Faller, équipe BCB (Biométaux et Chimie Biologique), Bertrand Vileno (POMAM), Institut de Chimie, UMR 7177.