Site-Specific Protein Labeling in the Pharmaceutical Industry: Experiences from Novartis Drug Discovery

  • Lukas LederEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1266)


Chemically modified proteins play an important role in several fields of pharmaceutical R&D, starting from various activities in drug discovery all the way down to biopharmaceuticals with improved properties such as antibody–drug conjugates. In the first part of the present chapter the significance and use of labeled proteins in biophysical methods, biochemical and cellular assays, in vivo imaging, and biopharmaceuticals is reviewed in general. In this context, the most relevant methods for site-specific modification of proteins and their application are also described. In the second part of the chapter, in-house (Novartis) results and experience with different techniques for selective protein labeling are discussed, with a focus on chemical or enzymatic (Avi-tag) biotinylation of proteins and their application in biophysical and biochemical assays. It can be concluded that while modern methods of site-specific protein labeling offer new possibilities for pharmaceutical R&D, classical methods are still the mainstay mainly due to being well established. However, site-specific protein labeling is expected to increase in importance, in particular for antibody–drug conjugates and other chemically modified biopharmaceuticals.

Key words

Biophysical methods Biochemical assay Cellular assays In vivo imaging Biopharmaceutical Antibody–drug conjugates Biotin ligase Avi-tag SNAP-tag Transglutaminase Lipoic acid ligase Click chemistry Sortase Phosphopantetheinyl transferase 



I would like to thank the following colleagues: Jutta Blank, Marjo, Goette, Christian Bergsdorf, and Rainer Kneuer who gave valuable input and discussion in terms of performed experiments and general approaches in their respective field of expertise.


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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Center for Proteomic ChemistryNovartis Institutes for Biomedical ResearchBaselSwitzerland

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