A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry

K Alt; BM Paterson; E Westein; SE Rudd; SS Poniger; S Jagdale; K Ardipradja; TU Connell; GY Krippner; AKN Nair; X Wang; HJ Tochon-Danguy; PS Donnelly; K Peter; CE Hagemeyer

Journal article

A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry

K Alt, BM Paterson, E Westein, SE Rudd, SS Poniger, S Jagdale, K Ardipradja, TU Connell, GY Krippner, AKN Nair, X Wang, HJ Tochon-Danguy, PS Donnelly, K Peter, CE Hagemeyer

Angewandte Chemie International Edition | Published : 2015

DOI: 10.1002/anie.201411507

Abstract

A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron-emitting copper-64 radiotracer for fluorescence and positron-emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily a..

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University of Melbourne Researchers

Stacey Rudd Author

Xiaowei Wang Author

Paul Donnelly Author

Karlheinz Peter Author

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Grants

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by German Research Foundation

Awarded by National Heart Foundation

Funding Acknowledgements

This work was funded by the National Health and Medical Research Council (NHMRC), Grants 1029249, 1017670 and 1011418 as well as the Australian Research Council (P.S.D.). K.Al. is supported by the German Research Foundation (Al 1521/1-1). B.M.P. is supported by a Victorian Postdoctoral Research Fellowship funded by the Victorian Government. K.Ar. is supported by the NHMRC and the National Heart Foundation (586740). P.S.D. is an Australian Research Council Future Fellow. K.P. is a Principal Research Fellow of the NHMRC. C.E.H. is a National Heart Foundation Career Development Fellow. This research was undertaken using equipment provided by Monash Biomedical Imaging, Monash University as part of the Victorian Biomedical Imaging Capability (Victorian Government). The work was also supported in part by the Victorian Government's Operational Infrastructure Support Program, Victoria's Science Agenda Strategic Project Fund, and the PET Solid Target Laboratory, an ANSTO-Austin-LICR Cyclotron Partnership.