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Generation of glycan-specific nanobodies

MPG-Autoren
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Khilji,  Sana K.
Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Goerdeler,  Felix
Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

Frensemeier,  Kristin
Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

Warschkau,  David
Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Lühle,  Jost
Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

Fandi,  Zeinab
Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Schirmeister,  Falko
Daniel Kolarich, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Seeberger,  Peter H.
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Moscovitz,  Oren
Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Zitation

Khilji, S. K., Goerdeler, F., Frensemeier, K., Warschkau, D., Lühle, J., Fandi, Z., et al. (2022). Generation of glycan-specific nanobodies. Cell Chemical Biology. doi:10.1016/j.chembiol.2022.05.007.


Zitierlink: https://hdl.handle.net/21.11116/0000-000A-9CB8-7
Zusammenfassung
The development of antibodies that target specific glycan structures on cancer cells or human pathogens poses a significant challenge due to the immense complexity of naturally occurring glycans. Automated glycan assembly enables the production of structurally homogeneous glycans in amounts that are difficult to derive from natural sources. Nanobodies (Nbs) are the smallest antigen-binding domains of heavy-chain-only antibodies (hcAbs) found in camelids. To date, the development of glycan-specific Nbs using synthetic glycans has not been reported. Here, we use defined synthetic glycans for alpaca immunization to elicit glycan-specific hcAbs, and describe the identification, isolation, and production of a Nb specific for the tumor-associated carbohydrate antigen Globo-H. The Nb binds the terminal fucose of Globo-H and recognizes synthetic Globo-H in solution and native Globo-H on breast cancer cells with high specificity. These results demonstrate the potential of our approach for generating glycan-targeting Nbs to be used in biomedical and biotechnological applications.