Rapid Bioorthogonal Chemistry Turn-on through Enzymatic or Long Wavelength Photocatalytic Activation of Tetrazine Ligation

• Published in: Journal of the American Chemical Society Vol. 138; no. 18; pp. 5978 - 5983
• Main Authors: Zhang, Han, Trout, William S, Liu, Shuang, Andrade, Gabriel A, Hudson, Devin A, Scinto, Samuel L, Dicker, Kevin T, Li, Yi, Lazouski, Nikifar, Rosenthal, Joel, Thorpe, Colin, Jia, Xinqiao, Fox, Joseph M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.05.2016; Amer Chemical Soc
• Subjects: Adhesives; Catalysis; Chemistry; Chemistry, Multidisciplinary; Enzymes - chemistry; Heterocyclic Compounds, 1-Ring - chemistry; Horseradish Peroxidase - chemistry; Kinetics; Light; Methylene Blue - chemistry; Oxidation-Reduction; Photochemical Processes; Physical Sciences; Science & Technology; Spectrophotometry, Ultraviolet; OXIDATION; PHOTOCLICK CHEMISTRY; BIOCONJUGATION; IMPROVED STABILITY; CLICK CHEMISTRY; LIGHT; INDOLE-3-ACETIC ACIDS; TRANS-CYCLOOCTENE; HORSERADISH-PEROXIDASE; TOOL
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.6b02168

Rapid bioorthogonal reactivity can be induced by controllable, catalytic stimuli using air as the oxidant. Methylene blue (4 μM) irradiated with red light (660 nm) catalyzes the rapid oxidation of a dihydrotetrazine to a tetrazine thereby turning on reactivity toward trans-cyclooctene dienophiles. Alternately, the aerial oxidation of dihydrotetrazines can be efficiently catalyzed by nanomolar levels of horseradish peroxidase under peroxide-free conditions. Selection of dihydrotetrazine/tetrazine pairs of sufficient kinetic stability in aerobic aqueous solutions is key to the success of these approaches. In this work, polymer fibers carrying latent dihydrotetrazines were catalytically activated and covalently modified by trans-cyclooctene conjugates of small molecules, peptides, and proteins. In addition to visualization with fluorophores, fibers conjugated to a cell adhesive peptide exhibited a dramatically increased ability to mediate contact guidance of cells.