We herein introduce signal-responsive drug release from hydrogel scaffolds using nucleophilic signal sensitive prodrug linkers. This proof of concept is based on electron deficient azidophenyl allyl bromides, which enable facile prodrug development via nucleophilic substitution of tertiary amine drugs. An azido functionality on the molecular scaffold enables straightforward covalent conjugation to alkyne-substituted polymer gels. Simply mixing of clickable linker 1 with tertiary amine drugs in THF results in precipitation of prodrug products and circumvents lengthy synthesis procedures. Using this strategy, we were able to obtain prodrugs from a variety of drug precursors, e.g. anti-cancer, antibiotic, muscle relaxant, antidepressant or anesthetic, making this method not only easy to use but generally versatile and potentially widely applicable. We obtained control over drug activation kinetics by using S or