OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues.

Autor: Wang LG; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, USA., Montaño AR; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, USA., Combs JR; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, USA., McMahon NP; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, USA., Solanki A; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, USA., Gomes MM; Cancer Early Detection Advanced Research Center (CEDAR), Oregon Health & Science University, Portland, OR, USA.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Tao K; Cancer Early Detection Advanced Research Center (CEDAR), Oregon Health & Science University, Portland, OR, USA.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Bisson WH; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Szafran DA; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, USA., Samkoe KS; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.; Department of Surgery, Dartmouth Health, Lebanon, NH, USA., Tichauer KM; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA., Gibbs SL; Biomedical Engineering Department, Oregon Health & Science University, Portland, OR, USA. gibbss@ohsu.edu.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA. gibbss@ohsu.edu.
Jazyk: angličtina
Zdroj: Nature chemistry [Nat Chem] 2023 May; Vol. 15 (5), pp. 729-739. Date of Electronic Publication: 2023 Mar 30.
DOI: 10.1038/s41557-023-01173-6
Abstrakt: Non-destructive fluorophore diffusion across cell membranes to provide an unbiased fluorescence intensity readout is critical for quantitative imaging applications in live cells and tissues. Commercially available small-molecule fluorophores have been engineered for biological compatibility, imparting high water solubility by modifying rhodamine and cyanine dye scaffolds with multiple sulfonate groups. The resulting net negative charge, however, often renders these fluorophores cell-membrane-impermeant. Here we report the design and development of our biologically compatible, water-soluble and cell-membrane-permeable fluorophores, termed OregonFluor (ORFluor). By adapting previously established ratiometric imaging methodology using bio-affinity agents, it is now possible to use small-molecule ORFluor-labelled therapeutic inhibitors to quantitatively visualize their intracellular distribution and protein target-specific binding, providing a chemical toolkit for quantifying drug target availability in live cells and tissues.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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