Uchinomiya Shohei, Horobin Richard W, Alvarado-Martínez Enrique, Peña-Cabrera Eduardo, Chang Young-Tae
Department of Chemistry & MedChem Program, Life Sciences Institute, National University of Singapore, 117543, Singapore.
Comb Chem High Throughput Screen. 2016;19(5):378-83. doi: 10.2174/1386207319666160408150528.
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.
控制荧光染料在活细胞中的定位对于荧光成像至关重要。在此，我们描述了用于预测荧光染料细胞内定位的定量构效关系（QSAR）模型。为了生成QSAR模型，通过pKa计算的电荷（Z）、共轭键数（CBN）、最大共轭片段（LCF）、分子量（MW）和log P被用作参数。我们确定了119种BODIPY染料在活的NIH3T3细胞中的细胞内定位，并通过将模型预测与观察到的染料定位进行比较来评估模型的准确性。正如模型所预测的，没有BODIPY染料定位于细胞核或质膜。脂肪滴定位模型的准确率为92%，细胞质和溶酶体模型与观察到的染料定位的一致性较差，尽管远高于随机水平。因此，总体而言，QSAR模型在预测活细胞中染料定位方面的实用性得到了明确证明。
