3 years ago

Bioorthogonal Catalytic Activation Of Pt And Ru Anticancer Complexes By FAD And Flavoproteins

Aitziber Lopez Cortajarena, Silvia Alonso-de Castro, Luca Salassa, Fernando Lopez-Gallego
Recent advances in bioorthogonal catalysis promise to deliver new chemical tools for performing chemoselective transformations in complex biological environments. Herein we report how FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide) and four flavoproteins behave as unconventional photocatalysts capable of converting PtIV and RuII complexes into potentially toxic PtII or RuII-OH2 species. Using electron donors and low doses of visible light, the flavoproteins mini Singlet Oxygen Generator (miniSOG) and NADH oxidase (NOX) catalytically activate PtIV prodrugs with bioorthogonal selectivity. In the presence of NADH, NOX catalyzes PtIV activation in the dark as well, indicating for the first time that flavoenzymes may contribute to initiate the activity of PtIV chemotherapeutic agents.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201800288

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