1. Emission Tuning of Fluorescent Kinase Inhibitors: Conjugation Length and Substituent Effects.
- Author
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Dhuguru, Jyothi, Wenjun Liu, Gonzalez, Walter G., Babinchak, W. Michael, Miksovska, Jaroslava, Landgraf, Ralf, and Wilson, James N.
- Subjects
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KINASE inhibitors , *BIOCONJUGATES , *SUBSTITUENTS (Chemistry) , *FLUOROPHORES , *PROTEIN-tyrosine kinases , *QUINAZOLINE , *PHOTOEXCITATION , *OPTICAL spectroscopy - Abstract
Fluorescent N-phenyl-4-aminoquinazoline probes targeting the ATP-binding pocket of the ERBB family of receptor tyrosine kinases are reported. Extension of the aromatic quinazoline core with fluorophore "arms" through substitution at the 6-position of the quinazoline core with phenyl, styryl, and phenylbutadienyl moieties was predicted by means of TD-DFT calculations to produce probes with tunable photoexcitation energies and excited states possessing charge-transfer character. Optical spectroscopy identified several synthesized probes that are nonemissive in aqueous solutions and exhibit emission enhancements in solvents of low polarity, suggesting good performance as turn-on fluorophores. Ligand-induced ERBB2 phosphorylation assays demonstrate that despite chemical modification to the quinazoline core these probes still function as ERBB2 inhibitors in MCF7 cells. Two probes were found to exhibit ERBB2-induced fluorescence, demonstrating the utility of these probes as turn-on, fluoroescent kinase inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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