Pyrrole-imidazole polyamide (PIP) is a nuclease-resistant novel compound that inhibits gene expression through binding to the minor groove of DNA. Human aurora kinase-A (AURKA) and -B (AURKB) are important regulators in mitosis during the cell cycle. In this study, two specific PIPs (PIP-A and PIP-B) targeting AURKA and AURKB promoter regions were designed and synthesized, and their biological effects were investigated by several in vitro assays. PIP-A and PIP-B significantly inhibited the promoter activities, mRNA expression, and protein levels of AURKA and AURKB, respectively, in a concentration-dependent manner. Moreover, 1:1 combination treatment with both PIPs demonstrated prominent antiproliferative synergy (CI value [ED50] = 0.256) to HeLa cells as a result of inducing apoptosis-mediated severe catastrophe of cell-cycle progression. The novel synthesized PIP-A and PIP-B are potent and specific gene-silencing agents for AURKA and AURKB. © 2008 Elsevier Ltd. All rights reserved.
Takahashi, T., Asami, Y., Kitamura, E., Suzuki, T., Wang, X., Igarashi, J., … Hayashi, N. (2008). Development of Pyrrole-Imidazole Polyamide for Specific Regulation of Human Aurora Kinase-A and -B Gene Expression. Chemistry and Biology, 15(8), 829–841. https://doi.org/10.1016/j.chembiol.2008.06.006