Pyrrole-Imidazole Polyamides Distinguish Between Double-Helical DNA and RNA

摘要

Py-Im polyamides bind the minor groove of DNA in a sequence-specific manner, encoded by antiparallel side-by-side pairs of pyrrole (Py) and imidazole (Im) carbox-amides. Im/Py pairs distinguish the edge of a G·C base pair from C·G, Py/Py pairs are degenerate for T·A and A·T, and hydroxypyrrole/pyrrole pairs (Hp/Py) distinguish T·A from A-T base pairs. Hairpin Py-Im polyamides have been shown to bind specific DNA sequences with affinities typical of transcription factors.'4 Eight-ring oligomers are sufficiently small to permeate cell membranes, traffic to the nucleus, access chromatin, and disrupt protein-DNA interactions. Hairpin and cyclic Py-Im polyamides targeted to the androgen response element (ARE) have been shown to modulate expression of prostate-specific antigen (PSA) and other AR-driven genes.