Bioorthogonal fluorogenic dyes are indispensable tools in wash-free bioimaging of specific biological targets. However, the fluorogenicity of existing tetrazine-based bioorthogonal probes deteriorates as the emission wavelength shifts towards the NIR window, greatly limiting their applications in live cells and tissues. Herein, we report a generalizable molecular design strategy to construct ultra-fluorogenic dyes via a simple substitution at the meso-positions of various far-red and NIR fluorophores. Our probes demonstrate significant fluorescence turn-on ratios (10 -10 -fold) in the range 586-806 nm. These results will greatly expand the applications of bioorthogonal chemistry in NIR bioimaging and biosensing.
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http://dx.doi.org/10.1002/anie.202117386 | DOI Listing |
Chem Sci
January 2025
Department of Chemistry, Imperial College London Molecular Sciences Research Hub, 82 Wood Lane, White City Campus London W12 0BZ UK
The blood-brain-barrier prevents many imaging agents and therapeutics from being delivered to the brain that could fight central nervous system diseases such as Alzheimer's disease and strokes. However, techniques such as the use of stapled peptides or peptide shuttles may allow payloads through, with bioconjugation achieved bio-orthogonal tetrazine/norbornene click chemistry. A series of lanthanide-tetrazine probes have been synthesised herein which could be utilised in bio-orthogonal click chemistry with peptide-based delivery systems to deliver MRI agents through the blood-brain-barrier.
View Article and Find Full Text PDFChem Sci
January 2025
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University Beijing 100871 China
Protein lysine crotonylation has been found to be closely related to the occurrence and development of various diseases. Currently, site identification of crotonylation is mainly dependent on antibody enrichment; however, due to the cost, heterogeneity, and specificity of antibodies, it is desired to develop an alternative chemical tool to detect crotonylation. Herein, we report an alkynyl-functionalized bioorthogonal chemical probe, Cr-alkyne, for the detection and identification of protein lysine crotonylation in mammalian cells.
View Article and Find Full Text PDFChem Rev
January 2025
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14853, United States.
Cells contain thousands of different lipids. Their rapid and redundant metabolism, dynamic movement, and many interactions with other biomolecules have justly earned lipids a reputation as a vexing class of molecules to understand. Further, as the cell's hydrophobic metabolites, lipids assemble into supramolecular structures─most commonly bilayers, or membranes─from which they carry out myriad biological functions.
View Article and Find Full Text PDFBioorg Chem
February 2025
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China; College of Pharmacy, Dali University, Xia Guan, Dali, Yunnan 6710000, PR China. Electronic address:
Background: Tumor-specific molecular probe-based imaging strategies have shown great potential for tumor diagnosis. However, the sensitivity and contrast of imaging may interfere with the complex labeling process and degradation of tumor-specific imaging probes. We sought to adapt a pretargeting strategy and an in vivo bioorthogonal reaction to improve hyaluronan (HA)-based tumor multimodal imaging diagnosis.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Bioorthogonal chemistry-mediated self-assembly holds great promise for dynamic molecular imaging in living organisms. However, existing approaches are limited to nanoaggregates with 'always-on' signals, suffering from high signal-to-background ratio (SBR) and compromised detection sensitivity. Herein we report a nitrile-aminothiol (NAT) bioorthogonal fluorogenic probe (CyNA-SS-FK) for ultrasensitive diagnosis of orthotopic hepatocellular carcinoma.
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