Bioconjugation

Bioconjugation enables the covalent attachment of functional molecules to nanobodies, expanding their use in imaging, diagnostics, targeted delivery, biosensing and therapeutic development.

A successful nanobody conjugation strategy requires more than simply linking two molecules together.

The conjugation site, reaction chemistry, linker properties and payload-to-nanobody ratio can all influence product homogeneity, antigen-binding activity, solubility, stability and downstream performance.

At Jotbody, each project is designed according to the nanobody sequence, payload characteristics, intended application and analytical requirements.

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Nanobody Bioconjugation Approaches

Nanobody conjugation can be performed through residue-directed chemical modification or site-specific engineering. The optimal approach depends on the required conjugation ratio, product homogeneity, payload properties and downstream application.

Amine-Directed
Conjugation

A robust and widely applicable approach targeting accessible primary amines. Suitable for rapid feasibility studies, although it may generate heterogeneous conjugates.

Thiol-Directed
Conjugation

Engineered cysteine residues enable more controlled payload attachment and improved conjugate orientation.

Click Chemistry

Bioorthogonal reactions provide selective conjugation under mild conditions and support the preparation of well-defined nanobody conjugates.

Enzymatic and Tag-
Mediated Conjugation

Bioorthogonal reactions provide selective conjugation under mild conditions and support the preparation of well-defined nanobody conjugates.

Enzymatic and tag-mediated nanobody conjugation

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Random vs. Site-Specific Conjugation

Random conjugation targets naturally occurring reactive groups and is suitable for rapid and cost-effective development. However, it may produce conjugates with different modification sites and payload ratios.

Site-specific conjugation introduces a defined reactive residue or recognition tag at a selected position. This approach provides better control over payload orientation, conjugation ratio and batch-to-batch consistency, while reducing the risk of modifying the antigen-binding region.

Random Conjugation	Site-Specific Conjugation
Rapid development	Defined conjugation site
Minimal engineering	Controlled payload ratio
Variable loading	Improved homogeneity
Suitable for feasibility studies	Suitable for advanced development

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Bioconjugation