Site‐Specific Dual Labeling of Proteins on Cysteine Residues with Chlorotetrazines. Issue 33 (5th July 2018)

• Record Type: Journal Article
• Authors: Canovas, Coline; Moreau, Mathieu; Bernhard, Claire; Oudot, Alexandra; Guillemin, Mélanie; Denat, Franck; Goncalves, Victor
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 33(2018)
• Page Start: 10646
• Page End: 10650
• Publication Date: 2018-07-05
• Subjects: bioconjugation -- click chemistry -- cysteine -- protein engineering -- site-specific labeling; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201806053
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Two for one : A two‐step strategy enables the double modification of proteins on one cysteine residue. This approach takes advantage of the selective reaction of monosubstituted chlorotetrazines with thiols under mild conditions and their ability to undergo orthogonal inverse‐electron‐demand Diels–Alder reactions.