Pyrrole-Imidazole Polyamides as artificial genetic switches

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...

Solution-phase synthesis of pyrrole-imidazole polyamides.

Pyrrole-imidazole polyamides are DNA-binding molecules that are programmable for a large repertoire of DNA sequences. Typical syntheses of this class of heterocyclic oligomers rely on solid-phase methods. Solid-phase methodologies offer rapid assembly on a micromole scale sufficient for biophysical characterizations and cell culture studies. In order to produce gram-scale quantities necessary f...

Cyclic pyrrole-imidazole polyamides targeted to the androgen response element.

Hairpin pyrrole-imidazole (Py-Im) polyamides are a class of cell-permeable DNA-binding small molecules that can disrupt transcription factor-DNA binding and regulate endogenous gene expression. The covalent linkage of antiparallel Py-Im ring pairs with an gamma-amino acid turn unit affords the classical hairpin Py-Im polyamide structure. Closing the hairpin with a second turn unit yields a cycl...

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

Targeted derepression of the human immunodeficiency virus type 1 long terminal repeat by pyrrole-imidazole polyamides.

The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression.