The prodrug delivery and mutant tyrosinase-mediated conversion in transfected cells

摘要

Tyrosinase is the major enzyme involved in melanin production in eukaryotes catalyzing hydroxylation of L-tyrosine with the formation of L-DOPA and subsequent oxidation of DOPA to DOPAquinone~1. Tyrosinase is unique in that its expression in cells can be utilized for both prodrug-conversion in treatment of experimental melanoma~2 as well as a system for MR imaging of gene expression~3. The goal of the current study was to investigate tyrosinase expression and the liposomebased prodrug delivery system for glioma treatment. We applied tyrosinase mutagenesis to investigate whether deletions of tyrosinase C-terminal domains can result in a variant with a higher specific activity that can be utilized in treatment of the model tumor 9L gliosarcoma cells.