A recent work between two research unit in Grenoble, SyMMES and Département de Chimie Moléculaire (DCM) highlights the design of the most active synthetic NiSOD mimic reported to date. This peptide mimic was engineered from a biological motif, the Amino Terminal CuII- and NiII-binding (ATCUN) motif, which promotes a square-planar geometry for the nickel cation as in the active site of the enzyme. Taking advantage of the versatility of peptides, we could adjust the metal cation coordination sphere with sulfur and nitrogen donors to tune the metal-binding site for optimal catalytic activity.
Finally, the introduction of positive charges through arginine residues around the NiII center dramatically enhanced the catalytic rate for the dismutation of the negatively charged superoxide anion. This strategy yielded the most potent synthetic NiSOD mimic reported to date, in terms of catalytic efficacy and stability in water at physiological pH.
(© CEA)
This work paves the way for future refinement and optimization, emphasizing the peculiar importance of the three-dimensional position of the positive charges. Continued efforts in this area are expected to yield compelling catalysts with diverse applications, ranging from basic research to therapeutic applications relevant to oxidative stress-related diseases.