Tuneable thiol exchange linkers for traceless drug release applications in prodrugs and ADCs

We describe a versatile and tuneable thiol responsive linker system using thiovinylketones, which relies on the conjugate addition-elimination mechanism of Michael acceptors for the traceless release of therapeutics. In a proof-of-principle study, we translate our findings to exhibit potent thiol-cl...

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Bibliographic Details
Published inChemical communications (Cambridge, England) Vol. 6; no. 55; pp. 725 - 728
Main Authors Walther, Raoul, Park, Mahri, Ashman, Nicola, Welch, Martin, Carroll, Jason S, Spring, David R
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 04.07.2024
The Royal Society of Chemistry
Subjects
Chemistry
Conjugates
Drugs
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Summary:We describe a versatile and tuneable thiol responsive linker system using thiovinylketones, which relies on the conjugate addition-elimination mechanism of Michael acceptors for the traceless release of therapeutics. In a proof-of-principle study, we translate our findings to exhibit potent thiol-cleavable antibiotic prodrugs and antibody-drug conjugates. We describe a versatile and tuneable thiol responsive linker system using thiovinylketones, that relies on the conjugate addition-elimination mechanism of Michael acceptors for the traceless release of therapeutics.
Bibliography:https://doi.org/10.1039/d4cc01558d
Electronic supplementary information (ESI) available. See DOI
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Contributed equally to this work.
ISSN:1359-7345
1364-548X
1364-548X
DOI:10.1039/d4cc01558d