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.
Kashiwazaki
Gengo
G
Department of Chemistry, Graduate School of Science, and, Institute for integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8502, Japan.
Bando
Toshikazu
T
Shinohara
Ken-ichi
K
Minoshima
Masafumi
M
Nishijima
Shigeki
S
Sugiyama
Hiroshi
H
D000477:Alkylating Agents / Q000737:chemistry*; D000478:Alkylation; D020029:Base Pairing; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000737:chemistry; D004214:Distamycins / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D019169:Jurkat Cells; D009757:Nylons / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry*
D000477:Alkylating Agents; D004214:Distamycins; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; C030000:stallimycin; D004247:DNA; C096654:N-methylpyrrole; C018100:1-methylimidazole