ArticleBioorganic & medicinal chemistry letters2025
Tunable spontaneous release of a carboxylic acid via a β-eliminative cleavable linker.
Article in Bioorganic & medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Self-cleavable linkers offer controlled payload release without the need for external stimuli, making them valuable for applications in chemical biology and clinical settings. In this work, we expand the scope of the β-eliminative cleavable linkers developed by Santi and coworkers to include the release of carboxylic acids. We demonstrate that the half-life of the ensuing ester conjugates can be controlled by varying electron-withdrawal using a pendant aryl sulfone moiety. The nascent ester group hydrolyzes readily in mouse serum but is stable in human serum. This system offers a tunable, autonomous release mechanism that could enable the delivery of new payloads in therapeutic contexts.
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