We herein described the design and synthesis of the cyanopyridoimidazoles (CPIs) as new bioorthogonal click reagents toward 1,2-aminothiol groups. Kinetic and density functional theory-based studies of the synthetic compounds revealed that incorporating an electron-withdrawing substituent into the CPI scaffold lowers its lowest unoccupied molecular orbital energy, consequently increasing reactivity. Optimized CPI showed rapid reactivity and high stability in physiological conditions and has been demonstrated to be suitable for various radiotracer synthetic methods. Based on the new bioorthogonal reaction, a [Ga]Ga-labeled prostate-specific membrane antigen-targeted probe was successfully prepared for imaging of prostate cancer in an animal model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.bioconjchem.3c00496 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Singlets-Driven Photoredox Catalysts: Transforming Noncatalytic Red Fluorophores to Efficient Catalysts.
JACS Au
December 2024
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, United States.
Red-light absorbing photoredox catalysts offer potential advantages for large-scale reactions, expanding the range of usable substrates and facilitating bio-orthogonal applications. While many red-light absorbing/emitting fluorophores have been developed recently, functional red-light absorbing photoredox catalysts are scarce. Many photoredox catalysts rely on long-lived triplet excited states (triplets), which can efficiently engage in single electron transfer (SET) reactions with substrates.
View Article and Find Full Text PDFIn Vivo Self-Assembly of PROTACs by Bioorthogonal Chemistry for Precision Cancer Therapy.
Angew Chem Int Ed Engl
December 2024
China Pharmaceutical University, Department of Medicinal Chemistry, 211198, Nanjing, CHINA.
Proteolysis targeting chimeras (PROTACs) hold immense promise for targeted protein degradation; however, challenges such as off-target effects, poor drug-likeness properties, and the "hook effect" remain. This study introduces Nano-Click-formed PROTACs (Nano-CLIPTACs) for precise tumor protein degradation in vivo. Traditional PROTACs with high molecular weight were first divided into two smaller druglike precursors capable of self-assembling to form functional PROTACs through a bioorthogonal reaction.
View Article and Find Full Text PDFClick-and-Release Formation of Urea Bonds in Living Cells Enabled by Micelle Nanoreactors.
Angew Chem Int Ed Engl
December 2024
The development of innovative strategies enabling chemical reactions in living systems is of great interest for exploring and manipulating biological processes. Herein, we present a pioneering approach based on both bioorthogonal and confined chemistry for intracellular drug synthesis. Exploiting a click-to-release reaction, we engineered nanoparticles capable of synthesizing drugs within cellular environments through bioorthogonal reactions with cyclooctynes.
View Article and Find Full Text PDFConditional Relay Activation of Theranostic Prodrug by Pretargeting Bioorthogonal Trigger and Fluorescence-guided Visible Light Irradiation.
Angew Chem Int Ed Engl
December 2024
Suzhou Medical College of Soochow University, Department of Medicinal Chemistry, 199 Renai Road, Suzhou Industry Park, 215123, Suzhou, CHINA.
Bioorthogonalized light-responsive click-and-uncage platform has enabled precise cell surface engineering and timed payload release, but most of such photoactivatable prodrugs have "always-on" photoactivity leading to the dark toxicity. On the other hand, the conditionally activatable photocage is limited to the application of fluorogenic probe/photosensitizer liberation. Herein, we devise a conditionally activatable theranostic platform based on the tetrazine (Tz)-boron-dipyrromethene (BODIPY) construct, in which tetrazine serves as a quencher motif to disable both the fluorescence and photoresponsivity of BODIPY.
View Article and Find Full Text PDFClick chemistry-based dual nanosystem for microRNA-122 detection with single-base specificity from tumour cells.
J Nanobiotechnology
December 2024
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avenida de la Ilustración, 18016, Granada, Spain.
MicroRNAs (miRNAs) have been recognised as potential biomarkers due to their specific expression patterns in different biological tissues and their changes in expression under pathological conditions. MicroRNA-122 (miR-122) is a vertebrate-specific miRNA that is predominantly expressed in the liver and plays an important role in liver metabolism and development. Dysregulation of miR-122 expression is associated with several liver-related diseases, including hepatocellular carcinoma and drug-induced liver injury (DILI).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!