Lanthano-peptides as mimics of lanthanide methanol dehydrogenase enZYME – LnZYME

LnZYME aims to design well-folded lanthano-peptides able to reproduce the structure of the active-site of the sole enzyme known standing on lanthanide, the Lanthanide-Methanol DeHydrogenase (Ln-MDH). The few organic molecular mimics described so far failed to reproduce Ln-MDH activity. Better mimics may be obtained by using a peptide scaffold. These lanthano-peptides would combine the advantages of small molecules (synthetic, modularity of their structure) and of artificial enzymes (control of 1st and 2nd coordination spheres).
LnZYME combines the rational design of a well-chosen and modular scaffolds to accommodate Ln-MDH cofactors, the synthesis of original unnatural amino acids to address the question of cofactor insertion and orientation in the scaffold, and experimental validation that capitalizes on the physical properties of lanthanide (luminescence, magnetism). Last, the project is based on a set of sound preliminary results.
LnZYME will have a strong impact for the bio-inorganic community. Indeed, it aims at answering the question of predicting the synergy between a peptide scaffold, a metal ion, and an organic cofactor, which is a current challenge in the field.