title: Evaluation of PI polyamide conjugates with eight-base pair recognition and improvement of the aqueous solubility by PEGylation.
abstract: To investigate the effect of elongating base-pair (bp) recognition sequences, we synthesized N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates with eight-bp recognition (3-5). The DNA alkylating activities of conjugates 3-5 were evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with a 208-bp DNA fragment. Conjugates 3-5 showed high alkylating activities at nanomolar concentrations. We then addressed the following issue about PI conjugates. Generally, PI polyamide conjugates hardly dissolve in aqueous solution. To improve the aqueous solubility, by the introduction of hydrophilic groups, we synthesized PI polyamide conjugates that were modified with a seco-CBI moiety (6-11). Conjugates 9-11 that were modified by methoxypolyethylene glycol (PEG) 750 acquired moderate solubility and stability in aqueous solution. In addition, conjugates 10 and 11 had high cytotoxicity against A549 and DU145.
authors: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto 606-8502, Japan.
authors: Toshiki
authors: T
authors: Takagaki
authors: Toshikazu
authors: T
authors: Bando
authors: Masaaki
authors: M
authors: Kitano
authors: Kaori
authors: K
authors: Hashiya
authors: Gengo
authors: G
authors: Kashiwazaki
authors: Hiroshi
authors: H
authors: Sugiyama
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D020029:Base Pairing / Q000187:drug effects; D045744:Cell Line, Tumor; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D014867:Water; D011092:Polyethylene Glycols; C096654:N-methylpyrrole; C018100:1-methylimidazole