Liang Ma, Chao Wang, Zihao He, Biao Cheng, Ling Zheng and Kun Huang* Pages 3373 - 3396 ( 24 )
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.
Peptide-drug conjugates (PDCs), antibody-drug conjugates (ADCs), peptide, linker, payloads, drug design.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, The Central Hospital of Wuhan, Tongji Medical College; Huazhong University of Science and Technology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan