Why fluorescent probes for endoplasmic reticulum are selective: an experimental and QSAR-modelling study.
The basis of the selectivity of fluorochromes routinely used to visualize the endoplasmic reticulum (ER) in live cells remains obscure. To clarify this, interactions of living cells with fluorochromes of varied physicochemical properties were analyzed experimentally and numerically using a quantitative structure activity relationship analysis (QSAR). Routine selective ER probes were found to be amphipathic, lipophilic cations with moderate-sized conjugated systems. The moderately lipophilic character permits probe uptake by passive diffusion without nonspecific accumulation in biomembranes. The moderately amphipathic character favors uptake into the ER, perhaps owing to its high concentration of zwitterionic lipid head-groups. The QSAR model rationalizes the impractical character of some ER probes mentioned in the literature, and could permit design of novel ER probes with different emission colors. The possibility of using the QSAR model as a tool to predict the accumulation of xenobiotics in the ER of living cells is illustrated by the localization of certain antipsychotic drugs in cultured cells.
Institute of Biomedical & Life Sciences, West Medical Building, The University of Glasgow, Glasgow G12 8QQ, Scotland. Janet.Colston@btinternet.com
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Colston
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Horobin
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Rashid-Doubell
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Pediani
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Johal
D000818:Animals; D014150:Antipsychotic Agents / Q000032:analysis / Q000493:pharmacokinetics; D002412:Cations; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum; D005456:Fluorescent Dyes / Q000737:chemistry / Q000592:standards*; D057927:Hydrophobic and Hydrophilic Interactions; D008856:Microscopy, Fluorescence; D021281:Quantitative Structure-Activity Relationship; D015262:Xenobiotics / Q000032:analysis / Q000493:pharmacokinetics
D014150:Antipsychotic Agents; D002412:Cations; D005456:Fluorescent Dyes; D015262:Xenobiotics