Design and biological evaluation of synthetic retinoids: probing length vs. stability vs. activity
Design and biological evaluation of synthetic retinoids: probing length vs. stability vs. activity
复制标题
DOI：
10.1039/c3mb70273a
复制
发表时间：
2013-01-01
影响因子：
--
通讯作者：
Przyborski, Stefan
中科院分区：
文献类型：
--
作者：
Clemens, Graeme;Flower, Kevin R.;Przyborski, Stefan
全反式维甲酸(ATRA)被广泛用于指导培养干细胞的分化。全反式维甲酸在多能人胚胎癌细胞系TERA2.cl.SP12作用下，可诱导外胚层分化和神经细胞类型的形成。我们在这项研究中报告了ATRA的新型多烯链长类似物需要特定的链长才能引起EC细胞TERA2.CL.SP12的生物反应，其中合成的维甲酸AH61尤其活性，而且确实比ATRA更有活性。采用RT-PCR和傅立叶变换红外光谱(FT-IRMS)结合多元分析的方法，直接比较了合成的维甲酸AH61和天然维甲酸对TERA2.cl.SP12细胞的影响。本研究的分析结果也证实了合成的维甲酸AH61具有与全反式维甲酸相当或更强的生物活性。除此之外，AH61还具有比全反式维甲酸更大的化合物稳定性，因此避免了与胚胎干细胞一起使用时的氧化或分解问题。
All trans-retinoic acid (ATRA) is widely used to direct the differentiation of cultured stem cells. When exposed to the pluripotent human embryonal carcinoma (EC) stem cell line, TERA2.cl.SP12, ATRA induces ectoderm differentiation and the formation of neuronal cell types. We report in this study that novel polyene chain length analogues of ATRA require a specific chain length to elicit a biological responses of the EC cells TERA2.cl.SP12, with synthetic retinoid AH61 being particularly active, and indeed more so than ATRA. The impacts of both the synthetic retinoid AH61 and natural ATRA on the TERA2.cl.SP12 cells were directly compared using both RT-PCR and Fourier Transform Infrared Micro-Spectroscopy (FT-IRMS) coupled with multivariate analysis. Analytical results produced from this study also confirmed that the synthetic retinoid AH61 had biological activity comparable or greater than that of ATRA. In addition to this, AH61 has the added advantage of greater compound stability than ATRA, therefore, avoiding issues of oxidation or decomposition during use with embryonic stem cells.