Peptide–Drug Conjugates with Different Linkers for Cancer Therapy

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Drug conjugates are chemotherapeutic or cytotoxic agents covalently linked to targeting ligands such as an antibody or a peptide via a linker. While antibody–drug conjugates (ADCs) are now clinically established for cancer therapy, peptide–drug conjugates (PDCs) are gaining recognition as a new modality for targeted drug delivery with improved efficacy and reduced side effects for cancer treatment. The linker in a drug conjugate plays a key role in the circulation time of the conjugate and release of the drug for full activity at the target site. Herein, we highlight the main linker chemistries utilized in the design of PDCs and discuss representative examples of PDCs with different linker chemistries with the related outcome in cell and animal studies.


This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Medicinal Chemistry, volume 64, in 2021 following peer review. This article may not exactly replicate the final published version. The definitive publisher-authenticated version is available online at


American Chemical Society