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タイトル: | Effect of single pyrrole replacement with β-alanine on DNA binding affinity and sequence specificity of hairpin pyrrole/imidazole polyamides targeting 5'-GCGC-3'. |
著者: | Han, Yong-Woon Kashiwazaki, Gengo Morinaga, Hironobu Matsumoto, Tomoko Hashiya, Kaori Bando, Toshikazu Harada, Yoshie Sugiyama, Hiroshi https://orcid.org/0000-0001-8923-5946 (unconfirmed) |
著者名の別形: | 韓, 龍雲 |
キーワード: | Pyrrole–imidazole polyamide Sequence specificity Polyamide DNA binding small molecule |
発行日: | 1-Sep-2013 |
出版者: | Elsevier Ltd. |
誌名: | Bioorganic & medicinal chemistry |
巻: | 21 |
号: | 17 |
開始ページ: | 5436 |
終了ページ: | 5441 |
抄録: | N-Methylpyrrole (Py)-N-methylimidazole (Im) polyamides are small organic molecules that can recognize predetermined DNA sequences with high sequence specificity. As many eukaryotic promoter regions contain highly GC-rich sequences, it is valuable to synthesize and characterize Py-Im polyamides that recognize GC-rich motifs. In this study, we synthesized four hairpin Py-Im polyamides 1-4, which recognize 5'-GCGC-3' and investigated their binding behavior with surface plasmon resonance assay. Py-Im polyamides 2-4 contain two, one, and one β-alanine units, replacing the Py units of 1, respectively. The binding affinities of 2-4 to the target DNA increased 430, 390, and 610-fold, respectively, over that of 1. The association and dissociation rates of 2 to the target DNA were improved by 11 and 37-fold, respectively, compared with those of 1. Interestingly, the association and dissociation rates of 3 and 4 were higher than those of 2, even though the binding affinities of 2, 3, and 4 to the target DNA were comparable to each other. The binding affinity of 2 to DNA with a 2bp mismatch was reduced by 29-fold, compared with that to the matched DNA. Moreover, the binding affinities of 3 and 4 to the same mismatched DNA were reduced by 270 and 110-fold, respectively, indicating that 3 and 4 have greater specificities than 2 and are suitable as DNA-binding modules for engineered epigenetic regulation. |
著作権等: | © 2013 The Authors. Published by Elsevier Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
URI: | http://hdl.handle.net/2433/178656 |
DOI(出版社版): | 10.1016/j.bmc.2013.06.005 |
PubMed ID: | 23810670 |
出現コレクション: | 学術雑誌掲載論文等 |
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