Abstract 3533: DNA binding molecules as a new tool to regulate cancer cell fate

Abstract

Abstract Pyrrole-Imidazole (PI) polyamide molecule was originally designed from structures of natural DNA binding molecule, such as Distamicine and Diocarbamicine and has been discovered as a synthetic molecule which recognizes the minor groove of Watson-Click base pair of double-stranded DNA in a sequence-dependent manner. We have recently developed a semi-automatic synthesis system for PI polyamide, which are able to regulate specific target gene-expression under specific transcription factor binding inhibition for biological functional studies and perhaps patients’ therapy. PI polyamide immediately penetrated the nucleus in vitro and in vivo without any vehicle. After intra venous injection It rapidly reduce the serum concentration, delivered to most of tissue cells, excreted to urine or bile juice and did not metabolize in animals. The PI polyamides, designed for anti-Tgfb1 and anti-MMP9 activity, were well tolerated, reduced target gene expression and showed therapeutic effects in animal models of human diseases. For instance, when performed two studies using I.V. treatment by either of two independent anti-MMP9 polyamides, tumor metastasis was significantly suppressed in both studies using the same mouse model of human liver metastasis of colon cancer. This new auto-synthetic chemicals can be designed for many transcriptional regulation of transcripts and applied to prove many biological hypothesis of transcriptional regulation for cancer research, and may be used for cancer therapy in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3533. doi:10.1158/1538-7445.AM2011-3533