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Abstract
Dynamic covalent chemistry has emerged as a versatile synthetic tool for devising stable, stimuli-responsive bioconjugates. Nevertheless, dynamic covalent interactions often exhibit fast binding and dissociation events or vice versa, affecting their conversion rates or stabilities. To overcome this, we designed dual responsive peptide tags combining: (1) a pH responsive boronate ester with fast association and dissociation rates, and (2) a redox-active disulfide with slow formation and dissociation rate. Pre-coordination by boronic acid–catechol interaction improves self-sorting and selectivity in disulfide formation into heterodimers. The resulting bis-peptide conjugate exhibited improved complex stability in aqueous solution and acidic tumor-like extracellular microenvironment. The conjugate responds to pH changes and to a redox environment that is similar to certain conditions inside cancer cells. Such tags hold great promise for controlling the stability of bioconjugates under dilution in aqueous media, as well as designing intelligent pharmaceutics that react to distinct biological stimuli in cells.
Supplementary materials
Title
Dual stimuli-responsive dynamic covalent peptide tags for sequence-controlled bioconjugation and release
Description
Dynamic covalent chemistry has emerged as a versatile synthetic tool for devising stable, stimuli-responsive bioconjugates. Nevertheless, dynamic covalent interactions often exhibit fast binding and dissociation events or vice versa, affecting their conversion rates or stabilities. To overcome this, we designed dual responsive peptide tags combining: (1) a pH responsive boronate ester with fast association and dissociation rates, and (2) a redox-active disulfide with slow formation and dissociation rate. Pre-coordination by boronic acid–catechol interaction improves self-sorting and selectivity in disulfide formation into heterodimers. The resulting bis-peptide conjugate exhibited improved complex stability in aqueous solution and acidic tumor-like extracellular microenvironment. The conjugate responds to pH changes and to a redox environment that is similar to certain conditions inside cancer cells. Such tags hold great promise for controlling the stability of bioconjugates under dilution in aqueous media, as well as designing intelligent pharmaceutics that react to distinct biological stimuli in cells.
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