Sequence‐Specific DNA Alkylation by Tandem Py–Im Polyamide Conjugates

Tandem N‐methylpyrroleN‐methylimidazole (PyIm) polyamides with good sequence‐specific DNA‐alkylating activities have been designed and synthesized. Three alkylating tandem PyIm polyamides with different linkers, which each contained the same moiety for the recognition of a 10 bp DNA sequence, were evaluated for their reactivity and selectivity by DNA alkylation, using high‐resolution denaturing gel electrophoresis. All three conjugates displayed high reactivities for the target sequence. In particular, polyamide 1, which contained a β‐alanine linker, displayed the most‐selective sequence‐specific alkylation towards the target 10 bp DNA sequence. The tandem PyIm polyamide conjugates displayed greater sequence‐specific DNA alkylation than conventional hairpin PyIm polyamide conjugates (4 and 5). For further research, the design of tandem PyIm polyamide conjugates could play an important role in targeting specific gene sequences.