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

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Molecular Recognition of DNA Double Helix

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Abstract

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.

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Authors and Affiliations

  1. Institute Curie, Orsay, France

    Dr. Abhijit Saha

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  1. Dr. Abhijit Saha
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Correspondence to Abhijit Saha .

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Saha, A. (2018). Chemical Modification of a Synthetic Small Molecule Boosts Its Biological Efficacy Against Pluripotency Genes in Mouse Fibroblast. In: Molecular Recognition of DNA Double Helix. Springer Theses. Springer, Singapore. https://doi.org/10.1007/978-981-10-8746-2_3

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