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

Coline Canovas (1) , Mathieu Moreau (1) , Claire Bernhard (1) , Alexandra Oudot (2) , Mélanie Guillemin (2) , Franck Denat (1) , Victor Goncalves (1)

1 ICMUB - Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon]
2 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]

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.

Mots clés: bioconjugation; click chemistry; cysteine; protein engineering; site-specific labeling

Domaines: Chimie

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, 2018, 57 (33), pp.10646 - 10650. ⟨10.1002/anie.201806053⟩. ⟨hal-01857108⟩