%0 journal article %@ 1525-7797 %A Folikumah, M., Behl, M., Lendlein, A. %D 2021 %J Biomacromolecules %N 5 %P 1875-1884 %R doi:10.1021/acs.biomac.0c01690 %T Thiol–Thioester Exchange Reactions in Precursors Enable pH-Triggered Hydrogel Formation %U https://doi.org/10.1021/acs.biomac.0c01690 5 %X Bio-interactive hydrogel formation in situ requires sensory capabilities toward physiologically relevant stimuli. Here, we report on pH-controlled in situ hydrogel formation relying on latent cross-linkers, which transform from pH sensors to reactive molecules. In particular, thiopeptolide/thio-depsipeptides were capable of pH-sensitive thiol–thioester exchange reactions to yield α,ω-dithiols, which react with maleimide-functionalized multi-arm polyethylene glycol to polymer networks. Their water solubility and diffusibility qualify thiol/thioester-containing peptide mimetics as sensory precursors to drive in situ localized hydrogel formation with potential applications in tissue regeneration such as treatment of inflamed tissues of the urinary tract.