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

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.

Screenshot of the article Small-molecule probes for affinity-guided introduction of biocompatible handles on metal-binding proteins published Bioconjugate Chemistry

In this paper by M. R. Mortensen et al.,  an efficient and generic approach for the modification of metal-binding proteins with biocompatible chemical handles without the need for genetic modifications is reported. 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.

The paper has been published in Bioconjugate Chemistry. Link to the article Small-Molecule Probes for Affinity-Guided Introduction of Biocompatible Handles on Metal-Binding Proteins.