title: Prediction of Intracellular Localization of Fluorescent Dyes Using QSAR Models.
abstract: Control of fluorescent dye localization in live cells is crucial for fluorescence imaging. Here, we describe quantitative structure activity relation (QSAR) models for predicting intracellular localization of fluorescent dyes. For generating the QSAR models, electric charge (Z) calculated by pKa, conjugated bond number (CBN), the largest conjugated fragment (LCF), molecular weight (MW) and log P were used as parameters. We identified the intracellular localization of 119 BODIPY dyes in live NIH3T3 cells, and assessed the accuracy of our models by comparing their predictions with the observed dye localizations. As predicted by the models, no BODIPY dyes localized in nuclei or plasma membranes. The accuracy of the model for localization in fat droplets was 92%, with the models for cytosol and lysosomes showing poorer agreement with observed dye localization, albeit well above chance levels. Overall therefore the utility of QSAR models for predicting dye localization in live cells was clearly demonstrated.
authors.forename: Shohei
authors.initials: S
authors.lastname: Uchinomiya
authors.forename: Richard W
authors.initials: RW
authors.lastname: Horobin
authors.forename: Enrique
authors.initials: E
authors.lastname: Alvarado-Martínez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Peña-Cabrera
authors.affiliation: Department of Chemistry & MedChem Program, Life Sciences Institute, National University of Singapore, 117543, Singapore. chmcyt@nus.edu.sg.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
mesh_terms: D000818:Animals; D001896:Boron Compounds; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D021281:Quantitative Structure-Activity Relationship
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes