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Functional Fluorescently Labeled Bithiazole ΔF508-CFTR Corrector Imaged in Whole Body Slices in Mice
- Source :
- Bioconjugate Chemistry. 22:2593-2599
- Publication Year :
- 2011
- Publisher :
- American Chemical Society (ACS), 2011.
-
Abstract
- We previously reported the identification and structure-activity analysis of bithiazole-based correctors of defective cellular processing of the cystic fibrosis-causing CFTR mutant, ΔF508-CFTR. Here, we report the synthesis and uptake of a functional, fluorescently labeled bithiazole corrector. Following synthesis and functional analysis of four bithiazole-fluorophore conjugates, we found that 5, a bithazole-based BODIPY conjugate, had low micromolar potency for correction of defective δF508-CFTR cellular misprocessing, with comparable efficacy to benchmark corrector corr-4a. Intravenous administration of 5 to mice established its stability in extrahepatic tissues for tens of minutes. By fluorescence imaging of whole-body frozen slices, fluorescent corrector 5 was visualized strongly in gastrointestinal organs, with less in lung and liver. Our results provide proof-of-concept for mapping the biodistribution of a ΔF508-CFTR corrector by fluorophore labeling and fluorescence imaging of whole-body slices.
- Subjects :
- Boron Compounds
Biodistribution
Fluorescence-lifetime imaging microscopy
Fluorophore
Cystic Fibrosis
Stereochemistry
Whole body imaging
Biomedical Engineering
Cystic Fibrosis Transmembrane Conductance Regulator
Pharmaceutical Science
Bioengineering
Article
Mice
chemistry.chemical_compound
Animals
Whole Body Imaging
Fluorescent Dyes
Pharmacology
biology
Chemistry
Organic Chemistry
Fluorescence
Cystic fibrosis transmembrane conductance regulator
Thiazoles
Mutation
Biophysics
biology.protein
BODIPY
Biotechnology
Conjugate
Subjects
Details
- ISSN :
- 15204812 and 10431802
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Bioconjugate Chemistry
- Accession number :
- edsair.doi.dedup.....b2488582f67060400933b62f9fb8ee94