A fluorescent reporter of ATP binding-competent receptor kinases
| Autor: | Nirav V. Patel, Renaud Sicard, Ralf Landgraf, James N. Wilson, Jyothi Dhuguru, Wenjun Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Cell Survival Receptor ErbB-2 Clinical Biochemistry Pharmaceutical Science Breast Neoplasms Biochemistry Article chemistry.chemical_compound Adenosine Triphosphate ErbB Cell Line Tumor Drug Discovery Humans Binding site Phosphorylation Receptor Molecular Biology Fluorescent Dyes Binding Sites Chemistry Kinase Organic Chemistry Autophosphorylation Tyrosine phosphorylation Cell biology Spectrometry Fluorescence Protein kinase domain Quinazolines Molecular Medicine Female |
| Zdroj: | Bioorg Med Chem Lett |
| Popis: | ERBB receptor kinases play a crucial role in normal development and cancer malignancies. A broad range of modifications creates receptor subpopulations with distinct functional properties in live cells. Their apparent activation state, typically assayed by tyrosine phosphorylation of substrates, reflects a complex equilibrium of competing reactions. With the aim of developing optical tools to investigate ERBB populations and their state of activation, we have synthesized a fluorescent ‘turn-on’ probe, DMAQ, targeting the ERBB ATP binding pocket. Upon binding, probe emission increases due to the hydrophobic environment and restricted geometry of the ERBB2 kinase domain, facilitating the analysis of receptor states at low occupancy and without the removal of unbound probes. Cellular ERBB2 autophosphorylation is inhibited with saturation kinetics that correlate with the increase in probe fluorescence. Thus, DMAQ is an example of a new generation of ‘turn-on’ probes with potential applications in querying receptor kinase populations both in vitro and in live cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|