Peptide-Functionalized Luminescent Iridium Complexes for Lifetime Imaging of CXCR4 Expression
| Autor: | Patrick T. K. Chin, Fijs W. B. van Leeuwen, Kees Jalink, Aldrik H. Velders, Joeri Kuil, Joppe Oldenburg, Peter Steunenberg |
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| Rok vydání: | 2011 |
| Předmět: |
Receptors
CXCR4 Fluorescence-lifetime imaging microscopy Luminescence Cell Survival Pyridines Stereochemistry Gene Expression chemistry.chemical_element Breast Neoplasms Peptide Conjugated system Iridium Ligands Biochemistry Flow cytometry law.invention Coordination Complexes Cell surface receptor Confocal microscopy law Cell Line Tumor medicine Humans Receptor Molecular Biology Fluorescent Dyes chemistry.chemical_classification medicine.diagnostic_test Chemistry Organic Chemistry Flow Cytometry Molecular Imaging Kinetics Microscopy Fluorescence Biophysics Molecular Medicine Female Peptides Protein Binding |
| Zdroj: | ChemBioChem. 12:1897-1903 |
| ISSN: | 1439-4227 |
| Popis: | The chemokine receptor 4 (CXCR4) is over-expressed in 23 types of cancer in which it plays a role in, among others, the metastatic spread. For this reason it is a potential biomarker for the field of diagnostic oncology. The antagonistic Ac-TZ14011 peptide, which binds to CXCR4, has been conjugated to luminescent iridium dyes to allow for CXCR4 visualization. The iridium dyes are cyclometalated octahedral iridium(III) 2-phenylpyridine complexes that can be functionalized with one, two or three targeting Ac-TZ14011 peptides. Confocal microscopy and fluorescence lifetime imaging microscopy (FLIM) showed that the peptide-iridium complex conjugates can be used to visualize CXCR4 expression in tumor cells. The CXCR4 receptor affinity and specific cell binding of the mono-, di- and trimeric peptide derivatives were assessed by using flow cytometry. The three derivatives possessed nanomolar receptor affinity and could distinguish between cell lines with different CXCR4 expression levels. This yields the first example of a neutral iridium(III) complex functionalized with peptides for FLIM-based visualization of a cancer associated membrane receptor. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| Databáze: | OpenAIRE |
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