1. Turn-On Fluorescence Probe for Cancer-Related γ -Glutamyltranspeptidase Detection.
- Author
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Saleem M, Hanif M, Bonne S, Zeeshan M, Khan S, Rafiq M, Tahir T, Lu C, and Cai R
- Subjects
- Humans, Molecular Docking Simulation, Spectrometry, Fluorescence methods, Rhodamines chemistry, Animals, gamma-Glutamyltransferase metabolism, gamma-Glutamyltransferase chemistry, Fluorescent Dyes chemistry, Neoplasms diagnostic imaging, Neoplasms enzymology
- Abstract
The design and development of fluorescent materials for detecting cancer-related enzymes are crucial for cancer diagnosis and treatment. Herein, we present a substituted rhodamine derivative for the chromogenic and fluorogenic detection of the cancer-relevant enzyme γ -glutamyltranspeptidase (GGT). Initially, the probe is non-chromic and non-emissive due to its spirolactam form, which hinders extensive electronic delocalization over broader pathway. However, selective enzymatic cleavage of the side-coupled group triggers spirolactam ring opening, resulting in electronic flow across the rhodamine skeleton, and reduces the band gap for low-energy electronic transitions. This transformation turns the reaction mixture from colorless to intense pink, with prominent UV and fluorescence bands. The sensor's selectivity was tested against various human enzymes, including urease, alkaline phosphatase, acetylcholinesterase, tyrosinase, and cyclooxygenase, and showed no response. Absorption and fluorescence titration analyses of the probe upon incremental addition of GGT into the probe solution revealed a consistent increase in both absorption and emission spectra, along with intensified pink coloration. The cellular toxicity of the receptor was evaluated using the MTT assay, and bioimaging analysis was performed on BHK-21 cells, which produced bright red fluorescence, demonstrating the probe's excellent cell penetration and digestion capabilities for intracellular analytical detection. Molecular docking results supported the fact that probe-4 made stable interactions with the GGT active site residues.
- Published
- 2024
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