Article ; Online: Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.
2015 Volume 26, Issue 2, Page(s) 176–192
Abstract: Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past ... ...
| Abstract | Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering. |
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| MeSH term(s) | Animals ; Chemistry Techniques, Synthetic/methods ; Drug Discovery/methods ; Glycoconjugates/chemistry ; Glycoconjugates/genetics ; Humans ; Immunoconjugates/chemistry ; Immunoconjugates/genetics ; Models, Molecular ; Protein Engineering/methods |
| Chemical Substances | Glycoconjugates ; Immunoconjugates |
| Language | English |
| Publishing date | 2015-02-18 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Review |
| ZDB-ID | 1024041-x |
| ISSN | 1520-4812 ; 1043-1802 |
| ISSN (online) | 1520-4812 |
| ISSN | 1043-1802 |
| DOI | 10.1021/bc5004982 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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