Acyl Fluorides: Fast, Efficient, and Versatile Lysine-Based Protein Conjugation via Plug-and-Play Strategy.
Fiche publication
Date publication
avril 2017
Journal
Bioconjugate chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah, Dr WAGNER Alain, Dr KOLODYCH Sergii
Tous les auteurs :
Dovgan I, Ursuegui S, Erb S, Michel C, Kolodych S, Cianférani S, Wagner A
Lien Pubmed
Résumé
We report a plug-and-play strategy for the preparation of functionally enhanced antibodies with a defined average degree of conjugation (DoC). The first stage (plug) allows the controllable and efficient installation of azide groups on lysine residues of a native antibody using 4-azidobenzoyl fluoride. The second step (play) allows for versatile antibody functionalization with a single payload or combination of payloads, such as a toxin, a fluorophore, or an oligonucleotide, via copper-free strain-promoted azide-alkyne cycloaddition (SPAAC). It is notable that in comparison to a classical N-hydroxysuccinimide ester (NHS) strategy, benzoyl fluorides show faster and more efficient acylation of lysine residues in a PBS buffer. This translates into better control of the DoC and enables the efficient and fast functionalization of delicate biomolecules at low temperature.
Mots clés
Acylation, Alkynes, chemistry, Antibodies, Monoclonal, chemistry, Azides, chemistry, Benzyl Compounds, chemistry, Click Chemistry, Cycloaddition Reaction, Fluorescent Dyes, chemistry, Fluorides, chemistry, Humans, Immunoconjugates, chemistry, Lysine, chemistry, Molecular Structure, Oligonucleotides, chemistry, Receptor, ErbB-2, immunology, Succinimides, chemistry, Toxins, Biological, chemistry
Référence
Bioconjug. Chem.. 2017 Apr;: