ダウンロード数: 218
このアイテムのファイル:
ファイル | 記述 | サイズ | フォーマット | |
---|---|---|---|---|
j.bmc.2017.08.057.pdf | 510.94 kB | Adobe PDF | 見る/開く |
タイトル: | Evaluation of alkylating pyrrole-imidazole polyamide conjugates by a novel method for high-throughput sequencer |
著者: | Kashiwazaki, Gengo Maeda, Rina Kawase, Takashi Hashiya, Kaori Bando, Toshikazu Sugiyama, Hiroshi https://orcid.org/0000-0001-8923-5946 (unconfirmed) |
著者名の別形: | 前田, 里菜 橋谷, かおり 板東, 俊和 杉山, 弘 |
発行日: | 1-Jan-2018 |
出版者: | Elsevier Ltd |
誌名: | Bioorganic and Medicinal Chemistry |
巻: | 26 |
号: | 1 |
開始ページ: | 1 |
終了ページ: | 7 |
抄録: | N-Methylpyrrole-N-methylimidazole (PI) polyamides are a class of DNA minor groove binders with DNA sequence-specificity. DNA-alkylating PI polyamide conjugates are attractive candidates as anticancer drugs acting through DNA damage and its subsequent inhibition of cell proliferation. One example is a chlorambucil-PI polyamide conjugate targeting the runt-related transcription factor (RUNX) family. RUNX1 has pro-oncogenic properties in acute myeloid leukemia, and recently the chlorambucil-PI polyamide conjugate was demonstrated to have anticancer effects. Herein, we apply another DNA-alkylating agent, seco-CBI, to target the consensus sequence of the RUNX family. Two types of CBI conjugates were prepared and their binding properties were characterized by Bind-n-Seq analysis using a high-throughput sequencer. The sequencing data were analyzed by two methods, MERMADE and our new MR (motif identification with a reference sequence), and the resultant binding motif logos were as predicted from the pairing rules proposed by Dervan et al. This is the first report to employ the MR method on alkylating PI polyamide conjugates. Moreover, cytotoxicity of conjugates 3 and 4 against a human non-small cell lung cancer, A549, were examined to show promising IC[50]s of 120 nm and 63 nm, respectively. These findings suggest seco-CBI-PI polyamide conjugates are candidates for oncological therapy. |
著作権等: | © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ The full-text file will be made open to the public on 1 January 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/230869 |
DOI(出版社版): | 10.1016/j.bmc.2017.08.057 |
PubMed ID: | 29224995 |
出現コレクション: | 学術雑誌掲載論文等 |
このリポジトリに保管されているアイテムはすべて著作権により保護されています。