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A Reagent for Amine‐Directed Conjugation to IgG1 Antibodies
Author(s) -
Märcher Anders,
Palmfeldt Johan,
Nisavic Marija,
Gothelf Kurt V.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202013911
Subject(s) - reagent , chemistry , amine gas treating , moiety , selectivity , iminium , combinatorial chemistry , lysine , antibody , quinazolinone , conjugate , biochemistry , organic chemistry , ion , amino acid , catalysis , biology , immunology , mathematical analysis , mathematics
Abstract Functionalized antibodies are an indispensable resource for diagnosis, therapy and as a research tool for chemical biology. However, simpler and better methodologies are often required to improve the labeling of antibodies in terms of selectivity and scalability. Herein, we report the development of an easily available chemical reagent that allows site‐directed labeling of native human IgG1 antibodies in good yield and mono‐labeling selectivity. The salicylaldehyde moiety of the reagent reacts with surface exposed lysine residues to transiently form an iminium ion, and this positions a semi‐reactive ester in proximity of a second lysine residue that reacts with the ester to form an amide. Interestingly, it appears that the formation of the iminium ion also has a significant activating effect of the ester. We use flow cytometry and bio‐layer interferometry to confirm that the labeled antibodies retain antigen binding.