Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells
Angewandte Chemie - International Edition
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Lopes Bernardes, G. (2018). Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells. Angewandte Chemie - International Edition https://doi.org/10.1002/ange.201811338
Photo-activated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases, such as cancer. Herein, we describe a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and a photoinitiator. Importantly, we show that the activity of histone deacetylase inhibitor Largazole can be switched-off when stapled, but selectively switched-on when irradiated with non-phototoxic light in cancer cells.
Funded under the Royal Society (URF to G.J.L.B.), FCT Portugal (iFCT to G.J.L.B.), ERC StG (grant agreement No. 676832), D.G.I. MINECO/FEDER (CTQ2015-70524-R and RYC-2013-14706 to G.J.O.), Cambridge Trust and China Scholarship Council (PhD studentship to S.S.) and the EPSRC.
Engineering and Physical Sciences Research Council (EP/M003647/1)
The Royal Society (uf110046)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (702574)
European Research Council (676832)
Royal Society (URF\R\180019)
European Commission (EC) (852985)
External DOI: https://doi.org/10.1002/ange.201811338
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285696