Keggin-type polyoxotungstates as mushroom tyrosinase inhibitors - A speciation study

• Published in: Scientific reports 2019-03, Vol.9 (1), p.5183, Article 5183
• Main Authors: Breibeck, Joscha, Gumerova, Nadiia I., Boesen, Benedikt B., Galanski, Mathea Sophia, Rompel, Annette
• Format: Article
• Language: English
• Subjects: 140/131; 631/45/49/1141; 639/638/263/49/1141; 82/16; 82/83; Agaricales - enzymology; Anions; Aqueous solutions; Data processing; Enzyme Inhibitors - pharmacology; Enzymes; Humanities and Social Sciences; Hydrogen-Ion Concentration; Hydrolysis; Investigations; Kinetics; Magnetic Resonance Spectroscopy; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; multidisciplinary; NMR; Nuclear magnetic resonance; Oxidation; Polyphenol oxidase; Proteins; Reproducibility of Results; Science; Speciation; Tungsten Compounds - pharmacology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-41261-7

Mushroom tyrosinase ab PPO4 is a commercially relevant polyphenol oxidase and has been being targeted for numerous inhibition studies including polyoxometalates (POMs). In the present work, its diphenolase activity was inhibited at pH 6.8 by a series of structurally related polyoxotungstates (POTs) of the α-Keggin archetype, exhibiting the general formula [X n+ W 12 O 40 ] (8−n)− in order to elucidate charge-dependent activity correlations. Kinetic data were obtained from the dopachrome assay and 183 W NMR was applied to obtain crucial insights into the actual Keggin POT speciation in solution, facilitating a straightforward assignment of inhibition effects to the identified POT species. While [PW 12 O 40 ] 3− was completely hydrolyzed to its moderately active lacunary form H x [PW 11 O 39 ] (7−x)− ( K i  = 25.6 mM), [SiW 12 O 40 ] 4− showed the most pronounced inhibition effects with a K i of 4.7 mM despite of partial hydrolysis to its ineffective lacunary form H x [SiW 11 O 39 ] (8−x)− . More negative Keggin cluster charges of 5− and 6− generally resulted in preclusion of inhibitory efficacy as well as hydrolysis, but with the Ni-substituted cluster [PW 11 O 39 {Ni(H 2 O)}] 5− enzymatic inhibition was clearly restored ( K i  = 9.7 mM). The inhibitory capacity of the structurally intact Keggin POTs was found to be inversely correlated to their net charge. The here applied speciation strategy is of utmost importance for any biological POM application to identify the actually active POM species.