2645443-13-4Relevant articles and documents
Tetrazine Carbon Nanotubes for Pretargeted In Vivo “Click-to-Release” Bioorthogonal Tumour Imaging
Bernardes, Gon?alo J. L.,Conde, Jo?o,Guerreiro, Ana,Li, He
, p. 16023 - 16032 (2020)
The bioorthogonal inverse-electron-demand Diels–Alder (IEDDA) cleavage reaction between tetrazine and trans-cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single-walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ?SWCNTs) and a TCO-caged molecule was used to deliver active effector molecules. To optimize a turn-on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near-infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real-time, non-invasive tumour visualization with a high target-to-background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine-functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off-site activation of fluorophore/drug.
Doxorubicin prodrug as well as preparation method and application thereof
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Paragraph 0079; 0083-0084, (2021/09/01)
The invention relates to a doxorubicin prodrug as well as a preparation method and application thereof. The doxorubicin prodrug is doxorubicin modified by trans-cyclooctene and 6-maleimidohexanehydrazide trifluoroacetate. The preparation method comprises the following steps: reacting trans-cyclooctene p-nitrobenzene carbonate with doxorubicin in a solvent in a dark place to obtain a first product; and reacting the 6-maleimidohexanehydrazide trifluoroacetate with the first product in the solvent in a dark place to obtain the doxorubicin prodrug. Compared with a doxorubicin raw drug, the trans-cyclooctene is used for passivating the drug active sites of the doxorubicin in the spatial structure, so that the toxicity to cells can be remarkably reduced, and the side effects of the drug are reduced. Meanwhile, endogenous serum albumin is used as a drug carrier, so that the targeting property of the drug to tumors is realized. The preparation method of the doxorubicin prodrug is simple to operate, and the prepared doxorubicin prodrug has high chemical purity and relatively high yield.
A Bioorthogonal Click Chemistry Toolbox for Targeted Synthesis of Branched and Well-Defined Protein–Protein Conjugates
Baalmann, Mathis,Bitsch, Sebastian,Deweid, Lukas,Ilkenhans, Nadja,Kolmar, Harald,Neises, Laura,Schneider, Hendrik,Werther, Philipp,Wilhelm, Jonas,Wolfring, Martin,Wombacher, Richard,Ziegler, Michael J.
supporting information, p. 12885 - 12893 (2020/06/02)
Bioorthogonal chemistry holds great potential to generate difficult-to-access protein–protein conjugate architectures. Current applications are hampered by challenging protein expression systems, slow conjugation chemistry, use of undesirable catalysts, or often do not result in quantitative product formation. Here we present a highly efficient technology for protein functionalization with commonly used bioorthogonal motifs for Diels–Alder cycloaddition with inverse electron demand (DAinv). With the aim of precisely generating branched protein chimeras, we systematically assessed the reactivity, stability and side product formation of various bioorthogonal chemistries directly at the protein level. We demonstrate the efficiency and versatility of our conjugation platform using different functional proteins and the therapeutic antibody trastuzumab. This technology enables fast and routine access to tailored and hitherto inaccessible protein chimeras useful for a variety of scientific disciplines. We expect our work to substantially enhance antibody applications such as immunodetection and protein toxin-based targeted cancer therapies.
