Département de chimie moléculaire

The deciphering of the binding mode of tyrosinase (Ty) inhibitors is essential to understand how to regulate the tyrosinase activity. In this paper, by combining exptl. and theor. methods, we studied an unsym. tyrosinase functional model and its interaction with 2-hydroxypyridine-N-oxide (HOPNO), a new and efficient competitive inhibitor for bacterial Ty. The tyrosinase model was a dinuclear copper complex bridged by a chelated ring with two different complexing arms (namely (bis(2-ethylpyridyl)amino)methyl and (bis(2-methylpyridyl)amino)methyl). The geometrical asymmetry of the complex induces an unsym. binding of HOPNO. Comparisons have been made with the binding modes obtained on similar sym. complexes. Finally, by using quantum mechanics/mol. mechanics (QM/MM) calcns., we studied the binding mode in tyrosinase from a bacterial source. A new unsym. binding mode was obtained, which was linked to the second coordination sphere of the enzyme. [on SciFinder(R)]