A Versatile Approach for the Site-Specific Modification of Recombinant Antibodies Using a Combination of Enzyme-Mediated Bioconjugation and Click Chemistry.

2015-05-11

Alt, Karen

Paterson, Brett M

Westein, Erik

Rudd, Stacey E

Poniger, Stan S

Jagdale, Shweta

Ardipradja, Katie

Connell, Timothy U

Krippner, Guy Y

Nair, Ashish K N

Wang, Xiaowei

Tochon-Danguy, Henri J

Donnelly, Paul S

Peter, Karlheinz

Hagemeyer, Christoph E

Journal Article

10.1002/anie.201411507

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 adapted to incorporate a large array of tailor-made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules.

link

Angewandte Chemie (international Ed. in English) 2015; 54(26): 7515-9

Angewandte Chemie (International ed. in English)