Emission tuning of fluorescent kinase inhibitors: Conjugation length and substituent effects

Jyothi Dhuguru, Wenjun Liu, Walter G. Gonzalez, W. Michael Babinchak, Jaroslava Miksovska, Ralf Landgraf, James N Wilson

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4940-4947
Number of pages8
JournalJournal of Organic Chemistry
Volume79
Issue number11
DOIs
StatePublished - Jun 6 2014

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Phosphotransferases
Tuning
Quinazolines
Fluorophores
Phosphorylation
Photoexcitation
Chemical modification
Receptor Protein-Tyrosine Kinases
Excited states
Discrete Fourier transforms
Electron energy levels
Charge transfer
Assays
Substitution reactions
Adenosine Triphosphate
Fluorescence
Ligands

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Emission tuning of fluorescent kinase inhibitors : Conjugation length and substituent effects. / Dhuguru, Jyothi; Liu, Wenjun; Gonzalez, Walter G.; Babinchak, W. Michael; Miksovska, Jaroslava; Landgraf, Ralf; Wilson, James N.

In: Journal of Organic Chemistry, Vol. 79, No. 11, 06.06.2014, p. 4940-4947.

Research output: Contribution to journalArticle

Dhuguru, Jyothi ; Liu, Wenjun ; Gonzalez, Walter G. ; Babinchak, W. Michael ; Miksovska, Jaroslava ; Landgraf, Ralf ; Wilson, James N. / Emission tuning of fluorescent kinase inhibitors : Conjugation length and substituent effects. In: Journal of Organic Chemistry. 2014 ; Vol. 79, No. 11. pp. 4940-4947.
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