Chemical Modification of a Synthetic Small Molecule Boosts Its Biological Efficacy Against Pluripotency Genes in Mouse Fibroblast

  • Abhijit Saha
Part of the Springer Theses book series (Springer Theses)


Our synthetic transcriptional activator SAHA-PIP, Sδ (described here as 1), encompassing both sequence-specific pyrrole–imidazole polyamides (PIPs) and an epigenetic activator (SAHA) was shown to induce the endogenous expression of core pluripotency genes in mouse embryonic fibroblasts (MEFs). However, the expression levels of pluripotency genes by 1 in MEFs were relatively lesser than that in mouse embryonic stem (ES) cells. Here, in this chapter, we carried out studies to improve the efficacy of 1 and show that the biological activity of 1 got significantly (P ≤ 0.05) improved against the core pluripotency genes after the incorporation of an isophthalic acid (IPA) in its C-terminus. The resultant IPA conjugate 2 dramatically induced Oct-3/4 to demonstrate a new chemical strategy for developing PIP conjugates as next-generation genetic switches.


Biological activity Cellular uptake Gene expression Polyamides Transcription 


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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Institute CurieOrsayFrance

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