Abhijit Saha1, Ganesh N. Pandian2, Shinsuke Sato2, Junichi Taniguchi1, Yusuke Kawamoto1, Kaori Hashiya1, Toshikazu Bando1, Hiroshi Sugiyama3,1,2
1Department of Science, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8501, Japan
2Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo, Kyoto 606-8502 (Japan)
3CREST, Japan Science and Technology Corporation (JST), Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan
Tóm tắt
AbstractA 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 suggested Oct‐3/4 as 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 induced Oct‐3/4 and demonstrated a new chemical strategy for developing PIP conjugates as next‐generation genetic switches.
