Article
Chemistry, Multidisciplinary
Luping Liu, Dongyang Zhang, Mai Johnson, Neal K. Devaraj
Summary: In this study, we demonstrate a versatile approach to achieve spatial and temporal control of bioorthogonal cycloaddition reactions in living mammalian cells using light-activated formation of tetrazines. This method allows for precise labeling and modification with high degree of flexibility in cells.
Article
Chemistry, Multidisciplinary
Muyun Xu, Xinrui Ma, Jessica E. Pigga, He Zhang, Shuli Wang, Weiling Zhao, Huaifu Deng, Anna M. Wu, Rihe Liu, Zhanhong Wu, Joseph M. Fox, Zibo Li
Summary: We developed a hydrophilic F-18-labeled α-TCO derivative [F-18]3 through a simple reaction. [F-18]3 can be used to construct various PET agents and imaging probes.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Rocio Garcia-Vazquez, Umberto M. Battisti, Jesper T. Jorgensen, Vladimir Shalgunov, Lars Hvass, Daniel L. Stares, Ida N. Petersen, Francois Crestey, Andreas Loeffler, Dennis Svatunek, Jesper L. Kristensen, Hannes Mikula, Andreas Kjaer, Matthias M. Herth
Summary: In this study, a simple, scalable, and reliable direct F-18 labeling procedure was developed and successfully applied to create a tetrazine-based imaging agent for pretargeting. The tracer showed promising characteristics that may qualify it for future clinical translation.
Article
Oncology
Hanna Tano, Maryam Oroujeni, Anzhelika Vorobyeva, Kristina Westerlund, Yongsheng Liu, Tianqi Xu, Daniel Vasconcelos, Anna Orlova, Amelie Eriksson Karlstrom, Vladimir Tolmachev
Summary: The study showed that shortening PNA probes can significantly increase the difference in accumulation of radiometals in tumor xenografts and in kidneys, potentially leading to more efficient cancer therapy. This affibody-mediated PNA-based pretargeting approach holds promise for radionuclide therapy of HER2-expressing tumors.
Article
Chemistry, Medicinal
Christoph Bredack, Martin R. Edelmann, Edilio Borroni, Luca C. Gobbi, Michael Honer
Summary: Bioorthogonal pretargeted imaging using antibody-based click chemistry is a viable approach for molecular imaging. The study successfully demonstrated the labeling of A beta plaques in vitro, ex vivo, and in vivo using a brain-penetrating antibody. Further experiments are needed to optimize the stability and reactivity of the reactants.
Article
Chemistry, Multidisciplinary
Walter Kuba, Barbara Sohr, Patrick Keppel, Dennis Svatunek, Viktoria Humhal, Berthold Stoger, Marion Goldeck, Jonathan C. T. Carlson, Hannes Mikula
Summary: Modified trans-cyclooctenes (TCO) can efficiently manipulate molecules in biological environments through bioorthogonal reactions with tetrazines (Tz). The development of click-cleavable TCO has advanced the field of in vivo chemistry and enabled the design of therapeutic strategies that are being used in clinical settings. A cleavable TCO linker is an important component of these strategies. However, only one member of this class has been developed so far, and its synthesis is complex. To overcome this limitation, a dioxolane-fused cleavable TCO linker (dcTCO) was developed, which can be prepared in just five steps. By studying the structure, reaction kinetics, stability, and hydrophilicity of dcTCO, its bioorthogonal application in the design of a caged prodrug was demonstrated, leading to a significant >1000-fold increase in cytotoxicity upon in-situ Tz-triggered cleavage.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Karuna Adhikari, Jonatan Dewulf, Christel Vangestel, Pieter van der Veken, Sigrid Stroobants, Filipe Elvas, Koen Augustyns
Summary: This study developed a series of fast-reacting fluorinated d-TCO derivatives and successfully achieved tumor-specific visualization through a pretargeted blocking approach. However, further optimization of the radiotracer is needed to enhance the tumor-to-background ratios for pretargeted imaging.
Article
Biochemistry & Molecular Biology
Patrick Keppel, Barbara Sohr, Walter Kuba, Marion Goldeck, Philipp Skrinjar, Jonathan C. T. Carlson, Hannes Mikula
Summary: Bond-cleavage reactions triggered by bioorthogonal tetrazine ligation have been used to chemically control the function of (bio)molecules and activate prodrugs. However, current methods for releasing phenols are limited. To address this issue, we developed a self-immolative linker that connects cleavable amines and phenols, allowing for controlled release of prodrugs.
Article
Biochemical Research Methods
Ambra Spampinato, Erika Kuzmova, Radek Pohl, Veronika Sykorova, Milan Vrabel, Tomas Kraus, Michal Hocek
Summary: A series of modified dNTPs with different linkers were designed and synthesized as substrates for DNA polymerase. The reactivity of these modified nucleotides and DNA was systematically tested and compared in click reactions. The longer linker was found to be crucial for efficient labeling. These modified dNTPs were transported into live cells and successfully used for staining DNA and imaging DNA synthesis within short time periods. This method provides a new approach for in cellulo metabolic labeling and imaging of DNA synthesis that overcomes previous limitations.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Tatsiana Auchynnikava, Antti Aarela, Heidi Liljenback, Juulia Jarvinen, Putri Andriana, Luciana Kovacs, Jarkko Rautio, Johan Rajander, Pasi Virta, Anne Roivainen, Xiang-Guo Li, Anu J. Airaksinen
Summary: Pretargeted concept in positron emission tomography (PET) utilizing radiotracers labeled with short-lived radionuclides is an elegant solution to study processes with slow pharmacokinetics. Radiotracers based on tetrazine ligation with trans-cyclooctene (TCO) have become a state-of-the-art for pretargeted PET imaging. F-18-Fluoroglycosylation is an indirect radiofluorination method preferred for labeling tetrazine scaffolds. This study reports the biological evaluation of [F-18]FDG-Tz as a tracer for pretargeted PET imaging of TCO-functionalized molecular spherical nucleic acids (MSNA) against human epidermal growth factor receptor 2 (HER2) mRNA. Evaluation in healthy mice showed favorable pharmacokinetics, quick blood clearance, urinary excretion, and absence of GLUT1 transportation. Successful pretargeted experiments with TCO-functionalized MSNA demonstrated higher tumor uptake compared to preclicked MSNA.
Article
Polymer Science
Sumit Dadhwal, Arnold Lee, Shailesh K. Goswami, Sarah Hook, Allan B. Gamble
Summary: In this study, a self-immolative PEG-aryl azide block copolymer and a non-responsive 4-fluoroaryl block copolymer were successfully synthesized through systematic investigation of the RAFT and ATRP methods. The ATRP method provided the desired polymers in a highly controlled manner, while the RAFT conditions led to higher levels of aryl azide polymer degradation. Stimuli-responsive aryl azide polymers/nanoparticles demonstrated non-cytotoxicity up to 200 μg/ml concentrations in preliminary in vitro cell viability studies.
JOURNAL OF POLYMER SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Gonzalo Rodriguez, Marcelo Fernandez, Mirel Cabrera, Marcos Tassano, Pablo Cabral, Marcos Couto, Hugo Cerecetto, Maria Fernanda Garcia
Summary: The reaction between [1,2,4,5]tetrazines and trans-cyclooctene is a powerful tool in bioorthogonal processes. In this study, we used fluorescent- and radio-labelled [1,2,4,5]tetrazines and pre-targeted trans-cyclooctene modified-antibody for diagnostics. We explored [1,2,4,5]tetrazines with different Tc-99m-coordination-moieties as hydrophilic functions and found that some of them efficiently coordinated the radionuclide, allowing recognition of cells that overexpress vascular endothelial growth factor (VEGF) by reacting with trans-cyclooctene modified-bevacizumab.
Article
Chemistry, Medicinal
Di Xiao, Yuhao Jiang, Junhong Feng, Qing Ruan, Qianna Wang, Guangxing Yin, Junbo Zhang
Summary: Novel bone imaging agents were developed by synthesizing bisphosphonate isocyanide derivatives and radiolabeling them with Tc-99m. The [Tc-99m] Tc-CNALN complex showed high stability and bone/background ratio, making it a promising bone-seeking agent.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)