Sortase-Mediated Site-Specific Conjugation and 89Zr-Radiolabeling of Designed Ankyrin Repeat Proteins for PET

Fay, Rachael; Törő, Imre; Schinke, Anna-Lena; Simic, Branko; Schaefer, Jonas V; Dreier, Birgit; Plückthun, Andreas; Holland, Jason P

doi:10.1021/acs.molpharmaceut.2c00136

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Fay, R., Törő, I., Schinke, A.-L., Simic, B., Schaefer, J. V., Dreier, B., Plückthun, A., & Holland, J. P. (2022). Sortase-Mediated Site-Specific Conjugation and 89Zr-Radiolabeling of Designed Ankyrin Repeat Proteins for PET. Molecular Pharmaceutics, 19(10), 3576–3585. https://doi.org/10.1021/acs.molpharmaceut.2c00136

Abstract

Designed ankyrin repeat proteins (DARPins) are genetically engineered proteins that exhibit high specificity and affinity toward specific targets. Here, the G3-DARPin, which binds the HER2/neu receptor, was site-specifically modified with enzymatic methods and 89Zr-radiolabeled for applications in positron emission tomography (PET). Sortase A transpeptidation was used to install a desferrioxamine B (DFO) chelate bearing a reactive triglycine group to the C-terminal sortase tag of the G3-DARPin, and 89Zr-radiolabeling produced a novel