Cyanopyridoimidazole/1,2-Aminothiol Click Reaction: A Novel Bioorthogonal Reaction for Synthesis of Radiotracers

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 C...

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Bibliographic Details
Published in:Bioconjugate chemistry 2024-01, Vol.35 (1), p.107-114
Main Authors: Sun, Yi-Chen, Shi, Wei-Xin, Kuo, Wei-Chieh, Hsiang, Yi-Rong, Lo, Wei-Lin, Chen, Liang-Cheng, Farn, Shiou-Shiow, Lin, Ya-Fan, Chen, Kuo-Ting
Format: Article
Language:English
Subjects:
Animal models
Animals
Chemical reactions
Chemical synthesis
Click Chemistry
Cycloaddition Reaction
Density functional theory
Humans
Male
Molecular orbitals
Prostate cancer
Prostatic Neoplasms
Radioactive tracers
Radiopharmaceuticals
Reagents
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Summary: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 8a 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 [67Ga]­Ga-labeled prostate-specific membrane antigen-targeted probe was successfully prepared for in vivo imaging of prostate cancer in an animal model.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.3c00496