Affinity-Based Methods for Site-Specific Conjugation of Antibodies

Overview

Journal Bioconjug Chem

Publisher American Chemical Society

Specialty Biochemistry

Date 2021 Aug 9

PMID 34369763

Citations 13

Authors

Emma von Witting

Sophia Hober

Sara Kanje

Affiliations

Soon will be listed here.

Abstract

Conjugation of various reagents to antibodies has long been an elegant way to combine the superior binding features of the antibody with other desired but non-natural functions. Applications range from labels for detection in different analytical assays to the creation of new drugs by conjugation to molecules which improves the pharmaceutical effect. In many of these applications, it has been proven advantageous to control both the site and the stoichiometry of the conjugation to achieve a homogeneous product with predictable, and often also improved, characteristics. For this purpose, many research groups have, during the latest decade, reported novel methods and techniques, based on small molecules, peptides, and proteins with inherent affinity for the antibody, for site-specific conjugation of antibodies. This review provides a comprehensive overview of these methods and their applications and also describes a historical perspective of the field.

Citing Articles

Lipid-Directed Covalent Labeling of Plasma Membranes for Long-Term Imaging, Barcoding and Manipulation of Cells.

Aknine N, Pelletier R, Klymchenko A JACS Au. 2025; 5(2):922-936.

PMID: 40017781 PMC: 11863151. DOI: 10.1021/jacsau.4c01134.

Development of a Versatile Cancer Vaccine Format Targeting Antigen-Presenting Cells Using Proximity-Based Sortase A-Mediated Ligation of T-Cell Epitopes.

Wang A, Brink H, Bouma R, Affandi A, Nijen Twilhaar M, Heijnen D Bioconjug Chem. 2024; 35(11):1805-1814.

PMID: 39511711 PMC: 11583207. DOI: 10.1021/acs.bioconjchem.4c00403.

First site-specific conjugation method for native goat IgG antibodies via glycan remodeling at the conserved Fc region.

Dolan M, Sadiki A, Wang L, Wang Y, Barton C, Oppenheim S Antib Ther. 2024; 7(3):233-248.

PMID: 39262442 PMC: 11384149. DOI: 10.1093/abt/tbae014.

Chemoselective Reagents for the Traceless Bioreversible Modification of Native Proteins.

Petri Y, FitzGerald F, Raines R Bioconjug Chem. 2024; 35(9):1300-1308.

PMID: 39206956 PMC: 11600989. DOI: 10.1021/acs.bioconjchem.4c00338.

Tumor versus Tumor Cell Targeting in Metal-Based Nanoparticles for Cancer Theranostics.

Urbano-Gamez J, Guzzi C, Bernal M, Solivera J, Martinez-Zubiaurre I, Caro C Int J Mol Sci. 2024; 25(10).

PMID: 38791253 PMC: 11121233. DOI: 10.3390/ijms25105213.

References

Kanje S, Hober S . In vivo biotinylation and incorporation of a photo-inducible unnatural amino acid to an antibody-binding domain improve site-specific labeling of antibodies. Biotechnol J. 2015; 10(4):564-74. DOI: 10.1002/biot.201400808. View

Yu F, Alesand V, Nygren P . Site-Specific Photoconjugation of Beta-Lactamase Fragments to Monoclonal Antibodies Enables Sensitive Analyte Detection via Split-Enzyme Complementation. Biotechnol J. 2018; 13(7):e1700688. DOI: 10.1002/biot.201700688. View

Hui J, Tsourkas A . Optimization of photoactive protein Z for fast and efficient site-specific conjugation of native IgG. Bioconjug Chem. 2014; 25(9):1709-19. PMC: 4166039. DOI: 10.1021/bc500305v. View

Khongorzul P, Ling C, Ullah Khan F, Ihsan A, Zhang J . Antibody-Drug Conjugates: A Comprehensive Review. Mol Cancer Res. 2019; 18(1):3-19. DOI: 10.1158/1541-7786.MCR-19-0582. View

Kleywegt G, Uhlen M, Jones T . Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG. Structure. 1995; 3(3):265-78. DOI: 10.1016/s0969-2126(01)00157-5. View

Pirzer T, Becher K, Rieker M, Meckel T, Mootz H, Kolmar H . Generation of Potent Anti-HER1/2 Immunotoxins by Protein Ligation Using Split Inteins. ACS Chem Biol. 2018; 13(8):2058-2066. DOI: 10.1021/acschembio.8b00222. View

Rosier B, Cremers G, Engelen W, Merkx M, Brunsveld L, de Greef T . Incorporation of native antibodies and Fc-fusion proteins on DNA nanostructures via a modular conjugation strategy. Chem Commun (Camb). 2017; 53(53):7393-7396. PMC: 5708335. DOI: 10.1039/c7cc04178k. View

McDonagh C, Turcott E, Westendorf L, Webster J, Alley S, Kim K . Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment. Protein Eng Des Sel. 2006; 19(7):299-307. DOI: 10.1093/protein/gzl013. View

Derrick J, Wigley D . Crystal structure of a streptococcal protein G domain bound to an Fab fragment. Nature. 1992; 359(6397):752-4. DOI: 10.1038/359752a0. View

10.

Dorman G, Prestwich G . Benzophenone photophores in biochemistry. Biochemistry. 1994; 33(19):5661-73. DOI: 10.1021/bi00185a001. View

11.

Beck A, Reichert J . Antibody-drug conjugates: present and future. MAbs. 2014; 6(1):15-7. PMC: 7098595. DOI: 10.4161/mabs.27436. View

12.

Yu C, Tang J, Loredo A, Chen Y, Jung S, Jain A . Proximity-Induced Site-Specific Antibody Conjugation. Bioconjug Chem. 2018; 29(11):3522-3526. DOI: 10.1021/acs.bioconjchem.8b00680. View

13.

Braisted A, Wells J . Minimizing a binding domain from protein A. Proc Natl Acad Sci U S A. 1996; 93(12):5688-92. PMC: 39121. DOI: 10.1073/pnas.93.12.5688. View

14.

Alves N, Mustafaoglu N, Bilgicer B . Oriented antibody immobilization by site-specific UV photocrosslinking of biotin at the conserved nucleotide binding site for enhanced antigen detection. Biosens Bioelectron. 2013; 49:387-93. DOI: 10.1016/j.bios.2013.05.052. View

15.

Cremers G, Rosier B, Riera Brillas R, Albertazzi L, de Greef T . Efficient Small-Scale Conjugation of DNA to Primary Antibodies for Multiplexed Cellular Targeting. Bioconjug Chem. 2019; 30(9):2384-2392. PMC: 6753658. DOI: 10.1021/acs.bioconjchem.9b00490. View

16.

Kanje S, Herrmann A, Hober S, Mueller L . Next generation of labeling reagents for quantitative and multiplexing immunoassays by the use of LA-ICP-MS. Analyst. 2016; 141(23):6374-6380. DOI: 10.1039/c6an01878e. View

17.

Zhou Q . Site-Specific Antibody Conjugation for ADC and Beyond. Biomedicines. 2017; 5(4). PMC: 5744088. DOI: 10.3390/biomedicines5040064. View

18.

Pavlinkova G, Rajagopalan K, Muller S, Chavan A, Sievert G, Lou D . Site-specific photobiotinylation of immunoglobulins, fragments and light chain dimers. J Immunol Methods. 1997; 201(1):77-88. DOI: 10.1016/s0022-1759(96)00214-1. View

19.

VanBrunt M, Shanebeck K, Caldwell Z, Johnson J, Thompson P, Martin T . Genetically Encoded Azide Containing Amino Acid in Mammalian Cells Enables Site-Specific Antibody-Drug Conjugates Using Click Cycloaddition Chemistry. Bioconjug Chem. 2015; 26(11):2249-60. DOI: 10.1021/acs.bioconjchem.5b00359. View

20.

Kanje S, von Witting E, Chiang S, Bryceson Y, Hober S . Site-Specific Photolabeling of the IgG Fab Fragment Using a Small Protein G Derived Domain. Bioconjug Chem. 2016; 27(9):2095-102. DOI: 10.1021/acs.bioconjchem.6b00346. View