Sequence-specific alkylation of DNA by pyrrole-imidazole polyamides through cooperative interaction.
We designed and synthesized an alkylating N-methylpyrrole (Py) -N-methylimidazole (Im) polyamide and l-(chloromethyl)-5-hydroxy-l,2-dihydro-3H benz[e]indole (seco-CBI) conjugate 1. DNA alkylating activities of conjugate 1 were evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with DNA fragment containing human telomere repeat sequence. These results revealed that simultaneous treatment of the DNA fragment with conjugate 1 and Distamycin A (Dist) alkylate at the 5(')-GGTTAGGGTTA-3' sequence effectively due to cooperative interaction. Moreover, this combination has achieved 11-base-pair (bp) recognition. Thus, it is suggested that the utilization of one alkylating agent possessing long Py-Im polyamide moiety and short Py-Im polyamide partner can be an expedient way to attain the extension and precision of the recognition of DNA sequence.
Kashiwazaki
Gengo
G
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Bando
Toshikazu
T
Sugiyama
Hiroshi
H
D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004214:Distamycins / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry*
D018906:Antineoplastic Agents, Alkylating; D004214:Distamycins; D007093:Imidazoles; D009757:Nylons; C030000:stallimycin; D004247:DNA