Sequence-Specific Alkylation by Y-Shaped and Tandem Hairpin Pyrrole–Imidazole Polyamides

✍ Scribed by Shunta Sasaki; Toshikazu Bando; Masafumi Minoshima; Ken-ichi Shinohara; Hiroshi Sugiyama

• Book ID: 102793796
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 676 KB
• Volume: 14
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.200700571

✦ Synopsis

Abstract

To extend the target DNA sequence length of the hairpin pyrrole–imidazole (Py–Im) polyamide 1, we designed and synthesized Y‐shaped and tandem hairpin Py–Im polyamides 2 and 3, which possess 1‐(chloromethyl)‐5‐hydroxy‐1,2‐dihydro‐3__H__‐benz[e]indole (seco‐CBI) as DNA‐alkylating moieties. High‐resolution denaturing polyacrylamide gel electrophoresis by using 5′‐Texas‐Red‐labeled 465 base pair (bp) DNA fragments revealed that conjugates 2 and 3 alkylated the adenine of the target DNA sequences at nanomolar concentrations. Conjugate 2 alkylated adenine N3 at the 3′ end of two 8 bp match sequences, 5′‐AATAACCA‐3′ (site A) and 5′‐AAATTCCA‐3′ (site C), while conjugate 3 recognized one 10 bp match sequence, 5′‐AGAATAACCA‐3′ (site A) in the 465 bp DNA fragments. These results demonstrate that seco‐CBI conjugates of Y‐shaped and tandem hairpin polyamides have extended their target alkylation sequences.