4.5 Article

Oxidation-labile linkers for controlled drug delivery

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2023.129264

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Bioconjugates; Linkers; Oxidative stress; Drug development

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The continuous symbiosis between chemical biology and drug discovery has led to the design of innovative bifunctional molecules for targeted and controlled drug delivery. Protein-drug and peptide-drug conjugates are popular approaches to achieve targeted delivery, selectivity, and efficacy. The selection of appropriate payloads and linkers is crucial for meeting the main goals of these bioconjugates, particularly in neurodegenerative diseases and certain cancer types where oxidative stress plays an important role. This mini-review covers the most relevant publications on oxidation-labile linkers.
The continuous symbiosis throughout chemical biology and drug discovery has led to the design of innovative bifunctional molecules for targeted and controlled drug delivery. Among the different tools, protein-drug and peptide-drug conjugates are trend approaches to achieve targeted delivery, selectivity and efficacy. To meet the main goals of these bioconjugates, the selection of the appropriate payloads and linkers is crucial, as they must provide in vivo stability, while they may also help to achieve the therapeutic target and action. In neurodegenerative diseases or some cancer types, where oxidative stress plays an important role, linkers sensitive to oxidative conditions may be able to release the drug once the conjugate achieves the target. Considering specially this specific application, this mini-review covers the most relevant publications on oxidation-labile linkers.

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