Selective cleavage of peptides and proteins is one of the most important procedures in analytical biochemistry. However, the extreme inertness of the amide bond with a half-life estimated to be up to 600 years at physiological pH and temperature makes this task highly challenging. Several proteolytic enzymes are available, but they are usually not regioselective and cleave proteins in short fragments which are difficult to identify. The few existing synthetic reagents require harsh conditions and even when applied in great excess over the substrate, they tend to cleave proteins with partial selectivity and low yields. Transition-metal and lanthanide ions are promising as new reagents for peptide bond cleavage since metal centers can coordinate to amide carbonyl oxygen atoms to polarize amide bonds. A prominent limitation, however, of using metal ions as catalysts for the hydrolysis reaction is the formation of gels at physiological and basic pH values. In the search for new artificial peptidases, metal-substituted polyoxometalates (POMs) have been intensively investigated in our research group for the hydrolysis of peptide bonds in peptides. In this study, Zr(IV) was incorporated into monolacunary Keggin anions [PW₁₁O₃₉]^7- to form a dimeric 2:2 Zr(IV)-substituted Keggin type POM, (Et₂NH₂)₈[{?-PW₁₁O₃₉Zr(à-OH)(H₂O)}₂]?7H₂O (1). The stability of the POM is highly dependent on pH, temperature, and its concentration, and can be monitored by ³¹P NMR spectroscopy. Various Gly-X, X-Gly, and X-Ser dipeptides were proven to be effectively hydrolyzed by 1 and their hydrolysis was highly dependent on the bulkiness and the nature of the side chain. The molecular mechanism of the peptide bond cleavage was elucidated based on combination of detailed kinetic experiments and multinuclear ¹H, ¹³C and ³¹P NMR spectroscopy.