Structure–activity relationships of various amino-hydroxy-benzenesulfonic acids and sulfonamides as tyrosinase substrates

• Published in: Biochimica et biophysica acta Vol. 1810; no. 8; pp. 799 - 807
• Main Authors: Rescigno, Antonio, Bruyneel, Frédéric, Padiglia, Alessandra, Sollai, Francesca, Salis, Andrea, Marchand-Brynaert, Jaqueline, Sanjust, Enrico
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2011
• Subjects: acids; Active site; active sites; Agaricales - enzymology; Benzenesulfonamide; Benzenesulfonic acid; Catalytic Domain; Enzyme Inhibitors - chemistry; enzyme substrates; Fungal Proteins - antagonists & inhibitors; Fungal Proteins - chemistry; high performance liquid chromatography; Kinetics; mass spectrometry; Molecular Structure; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - chemistry; mushrooms; oxidation; Phenoxazinone; spectrophotometers; Structure-Activity Relationship; structure-activity relationships; Sulfanilic Acids - chemistry; sulfonamides; Tyrosinase activity; Phenoxazinone; Benzenesulfonic acid; Tyrosinase activity; Active site; Benzenesulfonamide
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2011.05.002

o-Aminophenols have been long recognised as tyrosinase substrates. However their exact mode of interaction with the enzyme's active site is unclear. Properly vic-substituted o-aminophenols could help gain some insight into tyrosinase catalytic mechanism. Eight vic-substituted o-aminophenols belonging to two isomeric series were systematically evaluated as tyrosinase substrates and/or activators and/or inhibitors, by means of spectrophotometric techniques and HPLC-MS analysis. Some relevant kinetic parameters have also been obtained. Four o-aminophenolic compounds derived from 3-hydroxyorthanilic acid (2-amino-3-hydroxybenzenesulfonic acid) and their four counterparts derived from the isomeric 2-hydroxymetanilic acid (3-amino-2-hydroxybenzenesulfonic acid) were synthesised and tested as putative substrates for mushroom tyrosinase. While the hydroxyorthanilic derivatives were quite inactive as both substrates and inhibitors, the hydroxymetanilic compounds on the contrary all acted as substrates for the enzyme, which oxidised them to the corresponding phenoxazinone derivatives. Based on the available structures of the active sites of tyrosinases, the different affinities of the four metanilic derivatives for the enzyme, and their oxidation rates, we propose a new hypothesis regarding the interaction between o-aminophenols and the active site of tyrosinase that is in agreement with the obtained experimental results. [Display omitted] ► Two series of vic-substituted o-aminophenols were tested as tyrosinase substrates. ► Only hydroxymetanilic compounds were oxidised by the enzyme. ► A rationale for enzyme/substrate interaction in catalytic cycle was proposed.