Chemical Modification of a Synthetic Small Molecule Boosts its Biological Efficacy against Pluripotency Genes in Mouse Fibroblast.
Chemical Modification of a Synthetic Small Molecule Boosts its Biological Efficacy against Pluripotency Genes in Mouse Fibroblast.
复制标题
合成小分子的化学修饰提高了其针对小鼠成纤维细胞多能性基因的生物功效。
作者：
Saha;A.; Pandian;G. N.; Sato;S.; Taniguchi;J.; Kawamoto;Y.; Hashiya;K.; Bando;T.; Sugiyama;H.
最近发现，一种包含序列特异性吡咯-咪唑聚酰胺（PIP）和表观遗传激活剂（辛二酰苯胺异羟肟酸）的合成转录激活剂可以诱导小鼠胚胎成纤维细胞（MEF）中核心多能性基因的内源表达。微阵列数据分析表明Oct-3/4作为激活剂的可能靶途径。然而，用激活剂处理的MEF中的表达水平相对低于小鼠胚胎干细胞中的表达水平。在此，我们报告了为提高激活剂功效而进行的研究，结果表明，在 C 末端掺入间苯二甲酸 (IPA) 后，针对核心多能性基因的生物活性显着提高 (p<0.05)。由此产生的 IPA 结合物显着诱导了 Oct-3/4，并展示了开发 PIP 结合物作为下一代遗传开关的新化学策略。
A synthetic transcriptional activator encompassing both sequence‐specific pyrrole–imidazole polyamides (PIPs) and an epigenetic activator (suberoylanilide hydroxamic acid) was recently shown to induce the endogenous expression of core pluripotency genes in mouse embryonic fibroblasts (MEFs). Microarray data analysis suggestedOct‐3/4as the probable target pathway of the activator. However, the expression levels in MEFs treated with the activator were relatively lower than those in mouse embryonic stem cells. Herein, we report studies carried out to improve the efficacy of the activator and show that the biological activity was significantly (p<0.05) improved against the core pluripotency genes after the incorporation of an isophthalic acid (IPA) at the C terminus. The resultant IPA conjugate dramatically inducedOct‐3/4and demonstrated a new chemical strategy for developing PIP conjugates as next‐generation genetic switches.