| RRC ID |
18568
|
| 著者 |
Takagaki T, Bando T, Kitano M, Hashiya K, Kashiwazaki G, Sugiyama H.
|
| タイトル |
Evaluation of PI polyamide conjugates with eight-base pair recognition and improvement of the aqueous solubility by PEGylation.
|
| ジャーナル |
Bioorg Med Chem
|
| 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.
|
| 巻・号 |
19(19)
|
| ページ |
5896-902
|
| 公開日 |
2011-10-1
|
| DOI |
10.1016/j.bmc.2011.08.009
|
| PII |
S0968-0896(11)00633-X
|
| PMID |
21903400
|
| MeSH |
Antineoplastic Agents, Alkylating / chemical synthesis
Antineoplastic Agents, Alkylating / chemistry*
Antineoplastic Agents, Alkylating / toxicity
Base Pairing / drug effects
Cell Line, Tumor
Drug Design
Electrophoresis, Polyacrylamide Gel
Humans
Imidazoles / chemistry
Nylons / chemical synthesis
Nylons / chemistry*
Nylons / toxicity
Polyethylene Glycols / chemistry*
Pyrroles / chemistry
Solubility
Water / chemistry
|
| IF |
3.073
|
| 引用数 |
9
|
|
WOS 分野
|
CHEMISTRY, MEDICINAL
CHEMISTRY, ORGANIC
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
DU145(RCB2143) |
