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Near‐IR Light‐Mediated Cleavage of Antibody–Drug Conjugates Using Cyanine Photocages
Author(s) -
Nani Roger R.,
Gorka Alexander P.,
Nagaya Tadanobu,
Kobayashi Hisataka,
Schnermann Martin J.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201507391
Subject(s) - cyanine , cleavage (geology) , linker , conjugate , chemistry , cleave , combinatorial chemistry , small molecule , antibody drug conjugate , in vitro , bioconjugation , molecule , drug , biophysics , antibody , biochemistry , materials science , enzyme , organic chemistry , fluorescence , monoclonal antibody , computer science , biology , pharmacology , immunology , mathematics , mathematical analysis , fracture (geology) , composite material , operating system , quantum mechanics , physics
Despite significant progress in the clinical application of antibody drug conjugates (ADCs), novel cleavage strategies that provide improved selectivity are still needed. Herein is reported the first approach that uses near‐IR light to cleave a small molecule from a biomacromolecule, and its application to the problem of ADC linkage. The preparation of cyanine antibody conjugates, drug cleavage mediated by 690 nm light, and initial in vitro and in vivo evaluation is described. These studies provide the critical chemical underpinning from which to develop this near‐IR light cleavable linker strategy.