Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes

Boschanski M, Krüger T, Karsten L, Falck G, Alam S, Gerlach M, Muller B, Müller K, Sewald N, Dierks T (2021)
Bioconjugate chemistry.

Zeitschriftenaufsatz | E-Veröff. vor dem Druck | Englisch
 
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Abstract / Bemerkung
Multiple, site-specific protein conjugation is increasingly attractive for the generation of antibody-drug conjugates (ADCs). As it is important to control the number and position of cargoes in an ADC, position-selective generation of reactive sites in the protein of interest is required. Formylglycine (FGly) residues are generated by enzymatic conversion of cysteine residues embedded in a certain amino acid sequence motif with a formylglycine-generating enzyme (FGE). The addition of copper ions increases FGE activity leading to the conversion of cysteines within less readily accepted sequences. With this tuned enzyme activity, it is possible to address two different recognition sequences using two aerobic formylglycine-generating enzymes. We demonstrate an improved and facile strategy for the functionalization of a DARPin (designed ankyrin repeat protein) and the single-chain antibody scFv425-Fc, both directed against the epidermal growth factor receptor (EGFR). The single-chain antibody was conjugated with monomethyl auristatin E (MMAE) and carboxyfluorescein (CF) and successfully tested for receptor binding, internalization, and cytotoxicity in cell culture, respectively.
Erscheinungsjahr
2021
Zeitschriftentitel
Bioconjugate chemistry
eISSN
1520-4812
Page URI
https://pub.uni-bielefeld.de/record/2955530

Zitieren

Boschanski M, Krüger T, Karsten L, et al. Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes. Bioconjugate chemistry. 2021.
Boschanski, M., Krüger, T., Karsten, L., Falck, G., Alam, S., Gerlach, M., Muller, B., et al. (2021). Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes. Bioconjugate chemistry. https://doi.org/10.1021/acs.bioconjchem.1c00246
Boschanski, M., Krüger, T., Karsten, L., Falck, G., Alam, S., Gerlach, M., Muller, B., Müller, K., Sewald, N., and Dierks, T. (2021). Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes. Bioconjugate chemistry.
Boschanski, M., et al., 2021. Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes. Bioconjugate chemistry.
M. Boschanski, et al., “Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes”, Bioconjugate chemistry, 2021.
Boschanski, M., Krüger, T., Karsten, L., Falck, G., Alam, S., Gerlach, M., Muller, B., Müller, K., Sewald, N., Dierks, T.: Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes. Bioconjugate chemistry. (2021).
Boschanski, Mareile, Krüger, Tobias, Karsten, Lennard, Falck, Georg, Alam, Sarfaraz, Gerlach, Marcus, Muller, Benjamin, Müller, Kristian, Sewald, Norbert, and Dierks, Thomas. “Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes”. Bioconjugate chemistry (2021).

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