A benzylic linker promotes methyltransferase catalyzed norbornene transfer for rapid bioorthogonal tetrazine ligation. Issue 12 (20th October 2017)

• Record Type: Journal Article
• Authors: Muttach, F.; Muthmann, N.; Reichert, D.; Anhäuser, L.; Rentmeister, A.
• Is Part Of: Chemical science. Volume 8:Issue 12(2017)
• Page Start: 7947
• Page End: 7953
• Publication Date: 2017-10-20
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7sc03631k
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Benzylic AdoMet analogs enable highly efficient enzymatic transfer of norbornenes to nucleic acids and subsequent tetrazine ligation. Abstract : Site-specific alkylation of complex biomolecules is critical for late-stage product diversification as well as post-synthetic labeling and manipulation of proteins and nucleic acids. Promiscuous methyltransferases in combination with analogs of S -adenosyl-l -methionine (AdoMet) can functionalize all major classes of biomolecules. We show that benzylic moieties are transferred by Ecm1 with higher catalytic efficiency than the natural AdoMet. A relative specificity of up to 80% is achieved when a norbornene moiety is placed in para -position, enabling for the first time enzymatic norbornene transfer to specific positions in DNA and RNA— even in cell lysate. Subsequent tetrazine ligation of the stable norbornene moiety is fast, efficient, biocompatible and – in combination with an appropriate tetrazine – fluorogenic.