Bioorthogonal catalytic activation of Platinum and Ruthenium anticancer complexes by FAD and flavoproteins

Alonso de Castro, S. ; Cortajarena, A.L. ; López-Gallego, F. (Universidad de Zaragoza) ; Salassa, L.

Resumen: 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 act as unconventional photocatalysts capable of converting PtIV and RuII complexes into potentially toxic PtII or RuII-OH2 species. In the presence of 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 initiating the activity of PtIV chemotherapeutic agents.

Idioma: Inglés

DOI: 10.1002/anie.201800288

Año: 2018

Publicado en: Angewandte Chemie (International ed.) 57, 12 (2018), 3143-3147
ISSN: 1433-7851

Factor impacto JCR: 12.257 (2018)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 17 / 172 = 0.099 (2018) - Q1 - T1

Factor impacto SCIMAGO: 5.478 - Chemistry (miscellaneous) (Q1) - Catalysis (Q1)

Financiación: info:eu-repo/grantAgreement/EUR/COST/CM1303
Financiación: info:eu-repo/grantAgreement/EC/H2020/648071/EU/Protein-based functional nanostructures/ProNANO
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BES-2013-065642
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2015-69887-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2016-77367-C2-1-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/CTQ2016-80844-R

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)