ABSTRACT
Proteases are excellent biomarkers for a variety of diseases, offer multiple opportunities for diagnostic applications and are valuable targets for therapy. From a chemistry-based perspective this review discusses and critiques the most recent advances in the field of substrate-based probes for the detection and analysis of proteolytic activity both in vitro and in vivo.
Subject(s)
Peptide Hydrolases , Peptides , Biomarkers , Peptide Hydrolases/metabolism , Peptides/metabolism , ProteolysisABSTRACT
A ruthenium-based mitochondrial-targeting photosensitiser that undergoes efficient cell uptake, enables the rapid catalytic conversion of PtIV prodrugs into their active PtII counterparts, and drives the generation of singlet oxygen was designed. This dual mode of action drives two orthogonal cancer-cell killing mechanisms with temporal and spatial control. The designed photosensitiser was shown to elicit cell death of a panel of cancer cell lines including those showing oxaliplatin-resistance.
Subject(s)
Antineoplastic Agents/pharmacology , Organoplatinum Compounds/pharmacology , Photosensitizing Agents/pharmacology , Prodrugs/pharmacology , Singlet Oxygen/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Catalysis , Cell Death/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Organoplatinum Compounds/chemical synthesis , Organoplatinum Compounds/chemistry , Photochemical Processes , Photochemotherapy , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Prodrugs/chemical synthesis , Prodrugs/chemistry , Singlet Oxygen/chemistryABSTRACT
The term electroceutical has been used to describe implanted devices that deliver electrical stimuli to modify biological function. Herein, we describe a new concept in electroceuticals, demonstrating for the first time the electrochemical activation of metal-based prodrugs. This is illustrated by the controlled activation of Pt(iv) prodrugs into their active Pt(ii) forms within a cellular context allowing selectivity and control of where, when and how much active drug is generated.
