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タイトル: | Next-generation sequencing studies guide the design of pyrrole-imidazole polyamides with improved binding specificity by the addition of β-alanine. |
著者: | Anandhakumar, Chandran Li, Yue Kizaki, Seiichiro Pandian, Ganesh N Hashiya, Kaori Bando, Toshikazu Sugiyama, Hiroshi https://orcid.org/0000-0001-8923-5946 (unconfirmed) |
著者名の別形: | 杉山, 弘 |
キーワード: | DNA recognition high throughput screening next generation sequencing synthetic biology |
発行日: | 4-Nov-2014 |
出版者: | wiley |
誌名: | ChemBioChem |
巻: | 15 |
号: | 18 |
開始ページ: | 2647 |
終了ページ: | 2651 |
抄録: | The identification of binding sites for small molecules in genomic DNA is important in various applications. Previously, we demonstrated rapid transcriptional activation by our small molecule SAHA-PIP. However, it was not clear whether the strong biological effects exerted by SAHA-PIP were attributable to its binding specificity. Here, we used high-throughput sequencing (Bind-n-seq) to determine the binding specificity of SAHA-PIPs. Sequence specificity bias was determined for SAHA-PIPs (3 and 4), and this showed enhanced 6 bp sequence-specific binding compared with hairpin PIPs (1 and 2). This finding allowed us to investigate the role of the β-alanine that links SAHA to PIP, and led in turn to the design of ββ-PIPs (5 and 6), which showed enhanced binding specificity. Overall, we demonstrated the importance of β-moieties for the binding specificity of PIPs and the use of cost-effective high-throughput screening of these small molecules for binding to the DNA minor groove. |
著作権等: | This is the peer reviewed version of the following article: Anandhakumar, C., Li, Y., Kizaki, S., Pandian, G. N., Hashiya, K., Bando, T. and Sugiyama, H. (2014), Next-Generation Sequencing Studies Guide the Design of Pyrrole-Imidazole Polyamides with Improved Binding Specificity by the Addition of β-Alanine. ChemBioChem, 15: 2647–2651, which has been published in final form at http://dx.doi.org/10.1002/cbic.201402497. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. The full-text file will be made open to the public on 4 NOV 2015 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. 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。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/200257 |
DOI(出版社版): | 10.1002/cbic.201402497 |
PubMed ID: | 25371287 |
出現コレクション: | 学術雑誌掲載論文等 |
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