Synthesis and biological properties of pyrrole-imidazole polyamide conjugates.
We have developed a series of conjugates between pyrrole (Py)-imidazole (Im) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H benz[e]indole (seco-CBI) with an indole linker. High resolution polyacrylamide gel electrophoresis revealed that these conjugates alkylated DNA at predetermined sequences. Then, we demonstrated that conjugates 1 and 2 have DNA alkylation activities at double stranded human telomere sequence and potent cytotoxicities in cancer cell lines. In addition, we showed that conjugate 3 alkylates DNA with ten-base-pair recognition sequence in the presence of partner polyamide 4, which suggested alkylation through 3-4 heterodimer formation.
Minoshima
Masafumi
M
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo, Kyoto 606-8502, Japan.
Sasaki
Shunta
S
Fujimoto
Jun
J
Shinohara
Ken-Ichi
K
Bando
Toshikazu
T
Sugiyama
Hiroshi
H
D000478:Alkylation; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry
D018906:Antineoplastic Agents, Alkylating; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles