A trifunctional self-immolative spacer enables drug release with two non-sequential enzymatic cleavages
Alberto Dal Corso, Simone Arosio, Noemi Arrighetti, Paola Perego, Laura Belvisi, Luca Pignataro, Cesare Gennari
Abstract
Cyclative cleavage of an amine-carbamate self-immolative spacer to deliver a hydroxyl cargo was inhibited by spacer derivatisation with a phosphate monoester handle. This trifunctional spacer was installed in a model anticancer prodrug that showed fast drug release only when incubated with both a protease and a phosphatase enzyme.
Topics & Concepts
DephosphorylationProdrugChemistryEnzymeProteaseCombinatorial chemistryPhosphorylationDrugBiophysicsBiochemistryPhosphatasePharmacologyMedicineBiologyDendrimers and Hyperbranched PolymersRNA Interference and Gene DeliverySupramolecular Self-Assembly in Materials