Functional fluorescently labeled bithiazole ΔF508-CFTR corrector imaged in whole body slices in mice

Holly R. Davison, Stephanie Taylor, Chris Drake, Puay Wah Phuan, Nico Derichs, Chenjuan Yao, Ella F. Jones, Julie Sutcliffe, A. S. Verkman, Mark J. Kurth

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2593-2599
Number of pages7
JournalBioconjugate Chemistry
Volume22
Issue number12
DOIs
StatePublished - Dec 21 2011

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ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Davison, H. R., Taylor, S., Drake, C., Phuan, P. W., Derichs, N., Yao, C., Jones, E. F., Sutcliffe, J., Verkman, A. S., & Kurth, M. J. (2011). Functional fluorescently labeled bithiazole ΔF508-CFTR corrector imaged in whole body slices in mice. Bioconjugate Chemistry, 22(12), 2593-2599. https://doi.org/10.1021/bc2004457