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Bioconjug Chem. 2018 Sep 19;29(9):3016-3025. doi: 10.1021/acs.bioconjchem.8b00424. Epub 2018 Aug 23.

Small-Molecule Probes for Affinity-Guided Introduction of Biocompatible Handles on Metal-Binding Proteins.

Author information

1
Center for Multifunctional Biomolecular Drug Design at the Interdisciplinary Nanoscience Center , Aarhus University , Gustav Wieds Vej 14 , 8000 C , Aarhus , Denmark.
2
Department of Chemistry , Aarhus University , Langelandsgade 140 , 8000 C Aarhus , Denmark.
3
Department of Molecular Biology and Genetics , Aarhus University , Gustav Wieds Vej 10 , 8000 C Aarhus , Denmark.

Abstract

Protein conjugates of high heterogeneity may contain species with significantly different biological properties, and as a consequence, the focus on methods for production of conjugates of higher quality has increased. Here, we demonstrate an efficient and generic approach for the modification of metal-binding proteins with biocompatible chemical handles without the need for genetic modifications. Affinity-guided small-molecule probes are developed for direct conjugation to off-the-shelf proteins and for installing different chemical handles on the protein surface. While purification of protein conjugates obtained by small molecule conjugation is troublesome, the affinity motifs of the probes presented here allow for purification of the conjugates. The versatility of the probes is demonstrated by conjugation to several His-tagged and natural metal-binding proteins, including the efficient and area-selective conjugation to three therapeutically relevant antibodies.

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