Probing zinc-protein-chelant interactions using gold nanoparticles functionalized with zinc-responsive polypeptides

Abstract

The coordination of zinc by proteins and various other organic molecules is essential for numerous biological processes, such as in enzymatic catalysis, metabolism, and signal transduction. Presence of small molecular chelants can have a profound effect on the bioavailability of zinc and affect critical Zn 2+ -protein interactions. Zn 2+ chelators are also emerging therapeutics for Alzheimer's disease because of their preventive effect on zinc-promoted amyloid formation. Despite the importance of zinc-protein-chelant interactions in biology and medicine, probing such interactions is challenging. Here, an innovative approach is introduced for real-time characterization ofzinc-protein-chelant interactions using gold nanoparticles (AuNPs) functionalized with a zinc-responsive protein mimetic polypeptide. The peptidefunctionalized AuNPs aggregate extensively in the presence of Zn 2+ , triggered by specifi c Zn 2+ -mediated polypeptide dimerization and folding, causing a massive red shift of the plasmon band. Chelants affects the Zn 2+ -polypeptide interaction and thus the aggregation differently depending on their concentrations, zinc-binding affi nities, and coordination numbers, which affect the position of the plasmon band. This system is a simple and powerful tool that provides extensive information about the interactions of chelants in the formation of Zn 2+ coordination complexes, and an interesting platform for development of bioanalytical techniques, and characterization of chelationbased therapeutics.