A drug conjugate is a construct in which a pharmacologically active component is covalently joined to another molecular entity through a defined attachment or linker. The conjugation partner can provide a targeting function, alter physicochemical behaviour, or serve as a macromolecular carrier. Antibody conjugates combine antigen recognition with an attached payload, whereas polymer conjugates incorporate the drug into a polymer-associated molecular structure [1][2]. The attachment site and local chemical environment influence linker stability and the distribution of conjugate species in a preparation [3]. A cleavable linker contains a bond or sequence that releases the payload after a specified chemical or enzymatic transformation [4]. Other constructs undergo processing of the carrier to generate an active drug-containing product [1]. Drug loading, attachment-site occupancy, and the presence of unconjugated components contribute to molecular heterogeneity [1][3]. The intact conjugate, released payload, and resulting catabolites have distinct chemical identities and can differ in distribution, clearance, and interaction with biological targets [1][2][4].
- covalent conjugation
- antibody–drug conjugates
- payload release
- linker chemistry
References
- Alain Beck; Liliane Goetsch; Charles Dumontet; Nathalie Corvaïa; Strategies and challenges for the next generation of antibody–drug conjugates. Nat. Rev. Drug Discov. 2017, 16, 315-337, 10.1038/nrd.2016.268.
- Iriny Ekladious; Yolonda L. Colson; Mark W. Grinstaff; Polymer–drug conjugate therapeutics: advances, insights and prospects. Nat. Rev. Drug Discov. 2018, 18, 273-294, 10.1038/s41573-018-0005-0.
- Ben-Quan Shen; Keyang Xu; Luna Liu; Helga Raab; Sunil Bhakta; Margaret Kenrick; Kathryn L Parsons-Reponte; Janet Tien; Shang-Fan Yu; Elaine Mai; et al. Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat. Biotechnol. 2012, 30, 184-189, 10.1038/nbt.2108.
- Jonathan D. Bargh; Albert Isidro-Llobet; Jeremy S. Parker; David R. Spring; Cleavable linkers in antibody–drug conjugates. Chem. Soc. Rev. 2019, 48, 4361-4374, 10.1039/c8cs00676h.