Metal-Substituted Polyoxometalates as Artificial Peptidases.

Abstract

Selective hydrolytic cleavage of proteins has become an important procedure in numerous biochemical applications. Several transition metal and lanthanide complexes have long been known to effect the hydrolytic cleavage of unactivated amide bonds in proteins. Because they often operate under mild reaction conditions, the development of metal-based artificial peptidases has become an increasingly important area of research over the past decades.Within our lab, polyoxometalates (POMs) have been demonstrated to exhibit hydrolytic activity towards phosphoester bonds in RNA and DNA model systems. Inspired by studies reporting the interaction between POMs and proteins, we recently designed a conceptually new approach to the development of artificial peptidases by using POMs as ligands for various metal ions. Literature reports show that negatively charged POMs effectively bind to positively charged surface domains of the protein in a non-covalent, mainly electrostatic manner. Consequently, in our approach the POM does not only act as a ligand for the active metal ion, but is also responsible for the selectivity that is necessary for a controlled fragmentation of the polyamide backbone.In our study the Wells-Dawson POM was functionalized with various transition and lanthanide metal ions and their use as an artificial peptidase was examined on the dipeptide glycylglycine (GG). From all the metals under investigation Zr(IV) was selected and a detailed analysis of the hydrolysis of GG was given. This study was further extended to dipeptides with a Gly-X and X-Gly sequence in order to evaluate the influence of the X amino acid side chain. Furthermore, longer peptides were used and the hydrolytic activity of the synthesized POM was evaluated on ovalbumin and bovine serum albumin. These protein studies show that the POM selectively hydrolyses internal amide bonds in both proteins.nrpages: 172status: publishe