Abstract
We designed and synthesized alkylating conjugates 5– 7 and their partner N-methylpyrrole- N-methylimidazole (PI) polyamides 8, 9. The DNA alkylating activities of conjugates 5– 7 were evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with a 219 base pair (bp) DNA fragment containing the human telomere repeat sequence. Conjugate 5 efficiently alkylated the sequence, 5′-GGTTAGGGTT A-3′, in the presence of partner PI polyamide 8 or distamycin A (Dist). In contrast, the heterodimer system of 5 with 9 showed very weak alkylating activity. Accordingly, this heterotrimeric system of 5 with two short partners is an expedient way to attain improved precision and extension of the recognition of DNA sequences.
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