Development of Pyrrole-Imidazole (PI) Polyamides as

Disclosed is an inhibitor of the expression of CTGF gene, which comprises a pyrrole-imidazole polyamide. The pyrrole-imidazole polyamide has an N-methylpyrrole unit (hereinafter, referred to as “Py”), an N-methylimidazole unit (hereinafter, referred to as “Im”) and a ϝ-aminobutanoic acid unit. In the pyrrole-imidazole polyamide, the region of the ϝ-aminobutanoic acid unit is folded to form an U-shaped conformation in a miner groove of a double-helical region having a part or the entirety of a nucleotide sequence lying between position -195 to position -150 (SEQ ID NO:2) in a connective tissue growth factor (hereinafter, referred to as “CTGF”) promoter or a sequence complementary to the nucleotide sequence (hereinafter, the double-helical region is referred to a 'target region'). In the pyrrole-imidazole polyamide, a Pm/Im pair corresponds to a C-G base pair, an Im/Py pair corresponds to a G-C base pair, and a Py/Py pair corresponds to both an A-T base pair and a T-A base pair. 3. PI polyamides targeted to human LOX-1 gene (JP 2006-022063) http://jglobal.jst.go.jp/detail.php?JGLOBAL_ID=200903003017803187&q=&t=2 Gene silencing agent coronary atherosclerosis and stenosis for the drug-eluting stent 4. Automated solid-phase synthesis of PI polyamides (PCT/JP2006/322658, WO2007/060860) http://patent.ipexl.com/WO/2007ZZSLASHZZ060860.html Inventors: Noboru Fukuda, Syuzei Dohno, Hiroshi Sugiyama Original Assignees: Nihon University, Gentier Biosystems Incorporation Abstract: A synthesis method for PI polyamide is automated at a higher level and can produce a product with a high yield in a more stable manner. In a solid phase synthesis method, the automated synthesis of a polyimide can be promoted by using HCTU as a condensation-activator, the yield of a product can be increased by charging a monomer in a solid form, and a PI polyamide having any sequence can be synthesis by combining the synthesis method with a manual synthesis with an acid chloride. Compatible patents 1. Complex formation between dsDNA and oligomer of cyclic heterocycles US6472537B1 http://www.patentstorm.us/patents/6303312.html Inventors: Peter B. Dervan, Joel M. Gottesfeld