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A fluorescent photoprobe for the imaging of endothelin receptors.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2007 May-Jun; Vol. 18 (3), pp. 685-94. Date of Electronic Publication: 2007 Apr 07. - Publication Year :
- 2007
-
Abstract
- A novel fluorescent photoprobe for the imaging of endothelin A receptors (ET(A)R) was developed. Based on the nonpeptidyl, high-affinity, and selective ET(A)R antagonist 3-benzo[1,3]dioxol-5-yl-5-hydroxy-5-(4-methoxyphenyl)-4-(3,4,5-trimethoxybenzyl)-5H-furan-2-one (PD 156707), a modification of the lead structure with a PEG-spacer containing an amino moiety was performed. Labeling of this precursor with the fluorescent marker Cy 5.5 NHS-ester was accomplished by adaption of common peptide labeling procedures. The affinity of the Cy 5.5-labeled receptor antagonist was evaluated using human carcinoma cell lines with different degrees of ET(A)R expression. Fluorescence microscopy revealed that ET(A)R-positive MCF-7 human breast adenocarcinoma and HT-1080 human fibrosarcoma cells effectively bind the photoprobe at very low doses (nM), while ET(A)R-negative MDA-MB-435 human breast cancer cells showed no fluorescence signal. Binding specificity of the probe could be demonstrated by predosing with a specific ET(A)R antibody or the parent antagonist PD 156707 as a competing inhibitor. The results suggest that the modified photoprobe tightly binds to ET(A) receptors and thus may be a possible candidate for the imaging of ET(A)R-overexpressing tissues in vivo.
- Subjects :
- Carbocyanines chemical synthesis
Cell Line, Tumor
Dioxoles chemical synthesis
Fluorescent Dyes chemical synthesis
Humans
Receptor, Endothelin A metabolism
Carbocyanines chemistry
Carbocyanines metabolism
Dioxoles chemistry
Dioxoles metabolism
Fluorescent Dyes chemistry
Fluorescent Dyes metabolism
Neoplasms chemistry
Receptor, Endothelin A analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1043-1802
- Volume :
- 18
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17417816
- Full Text :
- https://doi.org/10.1021/bc060264w