Blocking Transcription Through a Nucleosome with Synthetic DNA Ligands

A Two-Hit Mechanism for Pre-Mitotic Arrest of Cancer Cell Proliferation by a Polyamide-Alkylator Conjugate

“…12,13,18,19 When bound within the coding region of a gene, polyamides do not represent an obstacle for elongating RNA polymerase, which can readily disrupt the polyamide/double-stranded DNA complex. 20 However, linkage of DNA-modifying agents to the polyamide, such as chlorambucil (Chl) 21 or CC-1065/CBI derivatives, 22 which covalently react with the DNA at the polyamide binding-site, can inhibit transcription by stalling RNA polymerase during elongation. 23 One concern for the use of polyamide-alkylator conjugates in cancer therapeutics is whether these molecules will discriminate between tumor and normal cells, which is the main problem with conventional DNA alkylators that are currently used in cancer therapy.…”

Development of a Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human Connective Tissue Growth Factor

“…[20][21][22][23] Synthetic PI polyamides can access their target sites in the nucleosome and may influence chromatin structure. 24,25) FITC-conjugated PI polyamide permeated cell membranes and accumulated and remained in all nuclei of cultured human HMCs. In comparison with our previous observations of the cellular distributions of antisense oligonucleotides and ribozymes, 11,12) the PI polyamide exhibited greater permeability and stability in cultured human HMCs.…”

Synthetic Pyrrole-Imidazole Polyamide Inhibits Expression of the Human Transforming Growth Factor-β1 Gene

“…Synthetic Py-Im polyamides can access their target sites in the nucleosome and may influence chromatin structure (Gottesfeld et al, 2001(Gottesfeld et al, , 2002. It has been reported that polyamide opens the heterochromatic brown satellite to allow binding of GAGA factor, resulting in a phenotypic change in Drosophila melanogaster.…”