More than 100 years ago, German physician Paul Ehrlich first proposed the concept
of selectively delivering “magic bullets” to tumors through targeting agents. The targeting
therapy with antibody-drug conjugates (ADCs) and peptide-drug conjugate (PDCs), which
are usually composed of monoclonal antibodies or peptides, toxic payloads and cleavage/
noncleavage linkers, has been extensively studied for decades. The conjugates enable
selective delivery of cytotoxic payloads to target cells, which results in improved efficacy,
reduced systemic toxicity and improved pharmacokinetics (PK)/pharmacodynamics (PD)
compared with traditional chemotherapy. PDC and ADC share similar concept, but with
vastly different structures and properties. Humanized antibodies introduce high specificity
and prolonged half-life, while small molecule weight peptides exhibit higher drug loading
and enhanced tissue penetration capacity, and the flexible linear or cyclic peptides are also
modified more easily. In this review, the principles of design, synthesis approaches and the
latest advances of PDCs are summarized.
Keywords: Peptide-drug conjugates (PDCs), antibody-drug conjugates (ADCs), peptide, linker, payloads, drug design.
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