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Site-Specific Dual Labeling of Proteins on Cysteine Residues with Chlorotetrazines

Abstract : Dual-labeled biomolecules constitute a new generation of bioconjugates with promising applications in therapy and diagnosis. Unfortunately, the development of these new families of biologics is hampered by the technical difficulties associated with their construction. In particular, the site specificity of the conjugation is critical as the number and position of payloads can have a dramatic impact on the pharmacokinetics of the bioconjugate. Herein, we introduce dichlorotetrazine as a trivalent platform for the selective double modification of proteins on cysteine residues. This strategy is applied to the dual labeling of albumin with a macrocyclic chelator for nuclear imaging and a fluorescent probe for fluorescence imaging.
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Coline Canovas, Mathieu Moreau, Claire Bernhard, Alexandra Oudot, Mélanie Guillemin, et al.. Site-Specific Dual Labeling of Proteins on Cysteine Residues with Chlorotetrazines. Angewandte Chemie International Edition, Wiley-VCH Verlag, 2018, 57 (33), pp.10646 - 10650. ⟨10.1002/anie.201806053⟩. ⟨hal-01857108⟩



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