Cooperative alkylation of double-strand human telomere repeat sequences by PI polyamides with 11-base-pair recognition based on a heterotrimeric design

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′-GGTTAGGGTTA-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.

We designed and synthesis of 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′-GGTTAGGGTTA-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.Figure optionsDownload as PowerPoint slide