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

Abstract:

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.

Authors:

R Walther, M Park, N Ashman, M Welch, JS Carroll, DR Spring

Journal:

Chem Commun (Camb)

Citation info:

60(55):7025-7028

Publication date:

4th Jul 2024

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