title: Peptide-Drug Conjugate: A Novel Drug Design Approach.
abstract: 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.
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan. China.
authors.forename: Zihao
authors.initials: Z
authors.lastname: He
authors.affiliation: The Central Hospital of Wuhan, Tongji Medical College; Huazhong University of Science and Technology. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001839:Bombesin / Q000737:chemistry; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D015195:Drug Design; D004357:Drug Synergism; D018796:Immunoconjugates / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D018796:Immunoconjugates; D009842:Oligopeptides; D010455:Peptides; D004364:Pharmaceutical Preparations; C047981:arginyl-glycyl-aspartic acid; D001839:Bombesin
keywords: Peptide-drug conjugates (PDCs); antibody-drug conjugates (ADCs); drug design; linker; payloads; peptide