Front Cover: Tetrazine‐Triggered Bioorthogonal Cleavage of trans‐Cyclooctene‐Caged Phenols Using a Minimal Self‐Immolative Linker Strategy (ChemBioChem 20/2022). (29th September 2022)

• Record Type: Journal Article
• Authors: Keppel, Patrick; Sohr, Barbara; Kuba, Walter; Goldeck, Marion; Skrinjar, Philipp; Carlson, Jonathan C. T.; Mikula, Hannes
• Is Part Of: Chembiochem. Volume 23:Number 20(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-29
• Subjects: bioorthogonal chemistry -- click chemistry -- cycloaddition -- elimination -- prodrugs; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200542
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract : Bioorthogonal prodrug activation : The cover feature, designed by co‐first author Barbara Sohr, illustrates the release of a phenolic drug triggered by the reaction of a trans ‐cyclooctene (TCO) conjugate with a tetrazine molecule (Tz). Key to the structural design is the incorporation of a self‐immolative linker (SIL) that 'dissolves' upon TCO/Tz click, enabling the development of bis(carbamate)‐linked conjugates with substantially improved stability under physiological conditions. Applying this strategy, we demonstrate the bioorthogonal cleavage of a TCO‐SIL‐caged prodrug via in situ reaction with Tz. Controlled release of an antimitotic drug induces depolymerization of microtubules, leading to a >200‐fold'turn‐on' in cytotoxicity. More information can be found in the Research Article by H. Mikula et al.