Biology of N-Methylpyrrole-N-methylimidazole Hairpin Polyamide

Development of Gene Silencing Pyrrole-Imidazole Polyamide Targeting the TGF-β1 Promoter for Treatment of Progressive Renal Diseases

“…Py-Im polyamides are resistant to nucleases and do not require particular delivery systems (4). Various types of sequence-specific DNA-binding Py-Im polyamides have been developed to regulate gene expression by targeting the promoter regions of enhancer and transcription factor binding elements (5). Binding of enhancers to the major and minor grooves of DNA can be inhibited by the minor groove-binding Py-Im polyamides (6).…”

Development of a molecule-recognized promoter DNA sequence for inhibition of HER2 expression

“…[8][9][10][11][12] A PI polyamide compound composed of the aromatic amino acids, N-methylpyrrole (Py) and N-methylimidazole (Im), is able to recognize the complementary DNA and bind to the minor groove in a sequence-specific manner because the Py-Im pair recognizes the complementary cytosine-guanine (C-G) and the Im-Py combination will bind to guanine-cytosine (G-C), respectively. [13][14][15][16][17] A pairing of Py-Py or b-alanine-b-alanine (b-b) binds to adenine-thymine or thymineadenine (A-T or T-A) base pairs. [14][15][16][17][18] The PI polyamide containing g-aminobutyric acid and N, N-dimethylaminopropylamine as an internal guide residue was found to specifically bind as a hairpin to be designated a target site with B300-fold enhancement relative to the binding affinities of the individual unlinked polyamide pair.…”

“…[13][14][15][16][17] A pairing of Py-Py or b-alanine-b-alanine (b-b) binds to adenine-thymine or thymineadenine (A-T or T-A) base pairs. [14][15][16][17][18] The PI polyamide containing g-aminobutyric acid and N, N-dimethylaminopropylamine as an internal guide residue was found to specifically bind as a hairpin to be designated a target site with B300-fold enhancement relative to the binding affinities of the individual unlinked polyamide pair. 18 In addition, this compound has a different character from other genesilencing tools, such as siRNA or antisense oligo nucleotides, because penetration in the living cells, cytosol import and nuclear transport of PI polyamide occur without any delivery system and may not be influenced by any catabolic enzymes or metabolic enzymes, such as nucleases and P450 enzymes, even in animals.…”

“…It has been reported that the binding ability of PI polyamide for a target sequence depends on the recognition for linear combination of Watson-Crick base pairs. 16 PI polyamide-HER2 should have approximately 13 000-50 000 capable target sites in a whole genome. Nevertheless, we think that the candidate-binding sites of PI polyamide-HER2 must be more restricted because of the selective recognition of PI polyamide-HER2 only at the non-histone binding to the minor groove region of double-helical DNA sequences.…”

Pyrrole-Imidazole Polyamides for Gene Therapy: Bioanalytical Methods and Pharmacokinetics

“…Synthetic polyamides recognize and bind to specific nucleotide sequences in the minor groove of double-helical DNA with high affinity (Pilch et al, 1996). Various sequencespecific DNA-binding PI polyamides have been developed to regulate gene expression by targeting the promoter regions of enhancer and transcription factor-binding elements in vitro (Murty et al, 2004). PI polyamides were first identified from duocarmycin A and distamycin A, which bind in the minor groove of DNA (Tao et al, 1999;Trauger et al, 1996).…”