Introduction of an Aldehyde Handle on Nanobodies by Affinity-Guided Labeling

Michael R. Mortensen, Mikkel B. Skovsgaard, Anders Märcher, Veronica L. Andersen, Johan Palmfeldt, Thorbjørn B. Nielsen, Thomas Tørring, Nick S. Laursen, Kasper R. Andersen, Jørgen Kjems, Kurt V. Gothelf

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


Chemically modified antigen-binding proteins are widely applied for their targeting abilities in the fields of biotechnology, medicine, and diagnostics. However, the production of site-selectively modified proteins remains a challenge. Here, we have designed a chemical probe for the introduction of a reactive aldehyde on nanobodies by metal-complex-guided conjugation. The probe design allows for purification of the conjugates, and the aldehyde constitutes an efficient handle for further modification of the nanobodies. In vitro experiments confirmed the binding activity and selectivity of fluorescent conjugates toward the native antigen. Furthermore, the modification strategy allowed for production of a nanobody-drug conjugate that was active in vitro.

Original languageEnglish
JournalBioconjugate Chemistry
Pages (from-to)1295-1300
Number of pages6
Publication statusPublished - May 2020


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