Dual Stimuli-Responsive Dynamic Covalent Peptide Tags: Toward Sequence-Controlled Release in Tumor-like Microenvironments

Dual responsive dynamic covalent peptide tags exhibiting cooperative effects are tailored to control stability of bioconjugates and their release in tumor-like microenvironment.

By exploiting pH responsive boronate ester with fast association and dissociation rates, and a redox-active disulfide with slow formation and dissociation rate, dual responsive peptide tags are devised. Such tags are integrated to therapeutic peptides or drugs to form intelligent bioconjugates. These conjugates exhibit improved stability and react to distinct biological stimuli in cells.