Identifying apoptotic cells with the 3-hydroxyflavone derivative F2N12S, a ratiometric fluorescent small molecule probe selective for plasma membranes: a possible general mechanism for selective uptake into apoptotic cells.
The mechanism of selective targeting of the plasma membrane of apoptotic cells by F2N12S, a recently reported ratiometric, fluorescent small molecule probe, was analyzed using decision-rule QSAR models. Selectivity was determined by a combination of the probe's weak amphiphilicity and slow flip-flop with the increased plasma membrane fluidity of apoptotic cells. The probable chemical features required for such probes may be defined in terms of numerical structural parameters as: 3.5 < AI < ∼ 5.5; log P < 5.0; HGS > 400 (where AI, log P and HGS parameters model amphiphilicity, lipophilicity and headgroup size, respectively). When HGS is <400, compounds are initially membrane selective, but subsequently are internalized.
Hope-Roberts
M
M
Institute of Interdisciplinary Research, Institute of Technical Translation, and Arcana Scientific and Medical Translations, Sheffield, UK. inst5@toucansurf.com
Horobin
R W
RW
Wainwright
M
M
D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D005419:Flavonoids / Q000032:analysis* / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000032:analysis* / Q000737:chemistry*; D006801:Humans; D008560:Membrane Fluidity; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling
C562294:F2N12S compound; D005419:Flavonoids; D005456:Fluorescent Dyes