The development of novel functional Py-Im polyamide conjugates for sequence-specific gene regulation

• Project/Area Number: 24310155
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Kyoto University
• Principal Investigator: Bando Toshikazu 京都大学, 理学(系)研究科(研究院), 准教授 (20345284)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: Py-Im ポリアミド / 特定遺伝子制御 / DNA塩基配列認識 / Py-Imポリアミド

Outline of Final Research Achievements

In our research, we developed novel functional Py-Im polyamide conjugates based on molecular design of DNA alkylating Py-Im polyamide conjugates.
In fact, we added various biological function to Py-Im polyamide conjugates in cell application by the chemical modification for the specific regulation of gene expression. And, we reported the results of our research.

Research Products

• [Journal Article] Selective Targeting of the KRAS Codon 12 Mutation Sequence by Pyrrole-Imidazole Polyamide seco-CBI Conjugates. (2016)
  • Author(s): Taylor RD, Chandran A, Kashiwazaki G, Hashiya K, Bando T, Nagase H and Sugiyama H.
  • Journal Title: Chemistry - A European Journal Volume: 21 Pages: 14996-15003
  • DOI: 10.1002/chem.201501870
  • NAID: 120005715311
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Novel Detection Technique of Polyamide Binding Sites by Photo-induced Electron Transfer in BrU Substituted DNA. (2015)
  • Author(s): Saha, A., Hashiya, F., Kizaki, S., Asamitsu, S., Hashiya, K., Bando, T., Sugiyama, H.
  • Journal Title: Chem. Commun. Volume: 51 Pages: 14485-14488
  • DOI: 10.1039/c5cc05104e
  • Peer Reviewed
• [Journal Article] A synthetic DNA-binding domain guides distinct chromatin-modifying small molecules to activate an identical gene network. (2015)
  • Author(s): Han, L., Pandian, G, N., Chandran, A., Sato, S., Taniguchi, J., Kashiwazaki, G., Sawatani, Y., Hashiya, K., Bando, T., Xu, Y., Qian, X., Sugiyama, H.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 54 Pages: 8700-8703
  • DOI: 10.1002/anie.201503607
  • NAID: 120006460099
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Synthetic Transcriptional Activator of Genes Associated with Retina in Human Dermal Fibroblasts. (2015)
  • Author(s): J. Syed, C. Anandhakumar, Ganesh N. Pandian, J. Taniguchi, S. Sato, K. Hashiya, G. Kashiwazaki, T. Bando, and H. Sugiyama
  • Journal Title: ChemBioChem. Volume: In press Pages: 1497-1501
  • DOI: 10.1002/cbic.201500140
  • NAID: 120005670900
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scars in a Common Marmoset Primat Model. (2015)
  • Author(s): Igarashi J, Fukuda N, Inoue T, Nakai S, Saito K, Fujiwara K, Matsuda H, Ueno T, Matsumoto Y, Watanabe T, Nagase H, Bando T Sugiyama H Itoh T Soma M.
  • Journal Title: PLOS. ONE Volume: 10(5)
  • DOI: 10.1371/journal.pone.0125295
  • NAID: 120005947168
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Integrating Epigenetic Modulators into Nanoscript for Enhances Chondrogenesis of Stem Cells. (2015)
  • Author(s): S. Patel, T. Pongkulapa, P. Yin, Ganesh N. Pandian, C. Rathnam, T. Bando, T. Vaijayanthi, H. Sugiyama and K-B. Lee.
  • Journal Title: J. Am. Chem. Soc. Volume: 137 Pages: 4598-4601
  • DOI: 10.1021/ja511298n
  • Peer Reviewed
• [Journal Article] Inhibition of Kras codon 12 mutants using a novel DNA-alkylating pyrrole-imidazole polyamide conjugate. (2015)
  • Author(s): Hiraoka K, Inoue T, Taylor RD, Watanabe T, Koshikawa N, Yoda H, Shinohara K, Takatori A, Sugimoto H, Maru Y, Denda T, Fujiwara K, Balmain A, Ozaki T, Bando T, Sugiyama H, Nagase H.
  • Journal Title: Nature Communications. Volume: 6 Pages: 6706-6706
  • DOI: 10.1038/ncomms7706
  • NAID: 120006460100
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tandem Trimer Pyrrole-Imidazole Polyamide Probes Targeting 18 Base Pairs in Human Telomere Sequence. (2015)
  • Author(s): Yusuke Kawamoto, Asuka Sasaki, Kaori Hashiya, Satoru Ide, Toshikazu Bando, Kazuhiro Maeshima, Hiroshi Sugiyama
  • Journal Title: Chem. Sci. Volume: 6 Pages: 2307-2312
  • DOI: 10.1039/c4sc03755c
  • NAID: 120005841416
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rational Design of Specific Binding Hairpin Py-Im Polyamides Targeting Human Telomere Sequences. (2015)
  • Author(s): Guo, C. X ., Kawamoto, Y., Asamitsu, S., Sawatani, Y., Hashiya, K., Bando, T., Sugiyama, H.
  • Journal Title: Bioorg. Med. Chem. Volume: 23 Pages: 855-860
  • DOI: 10.1016/j.bmc.2014.12.025
  • NAID: 120005555482
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Specific Alkylation of Human Telomere Repeat Sequences by a Tandem-Hairpin Motif of Pyrrole-Imidazole Polyamides with Indole-Seco-CBI. (2014)
  • Author(s): Yamamoto, M.; Bando, T.; Kawamoto, Y.; Taylor, R. D.; Hashiya, K.; Sugiyama, H.
  • Journal Title: Bioconjugate Chem. Volume: 25 Pages: 552-559
  • DOI: 10.1021/bc400567m
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sequence-specific DNA Alkylation by Tandem Py-Im Polyamide Conjugates. (2014)
  • Author(s): Taylor, R, D.; Kawamoto, Y.; Hashiya, K.; Bando, T.; Sugiyama, H.
  • Journal Title: Chem. Asian J. Volume: 9 Pages: 2527-2533
  • DOI: 10.1002/asia.201402331
  • NAID: 120005647509
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chemically modified synthetic small molecule boosts its biological efficacy against pluripotency genes in mouse fibroblast (2014)
  • Author(s): Saha, A.; Pandian, G. N.; Sato, S.; Taniguchi, J.; Kawamoto, Y.; Hashiya, K.; Bando, T.; Sugiyama, H.
  • Journal Title: ChemMedChem Volume: 9 Pages: 2374-2380
  • DOI: 10.1002/cmdc.201402117
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sequence-Specific DNA Alkylation and Transcriptional Inhibition by Long-Chain Hairpin Pyrrole-Imidazole Polyamide-Chlorambucil Conjugates Targeting CAG/CTG Trinucleotide Repeats. (2014)
  • Author(s): Asamitsu, S.; Kawamoto, Y.; Hashiya, F.; Hashiya, K.; Yamamoto, M.; Kizaki, S.; Bando, T.; Sugiyama, H.
  • Journal Title: Bioorg. Med. Chem. Volume: 22 Pages: 4646-4657
  • DOI: 10.1016/j.bmc.2014.07.019
  • NAID: 120005474526
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Targeted Suppression of EVI1 Oncogene Expression by Sequence-Specific Pyrrole-imidazole Polyamide. (2014)
  • Author(s): Junetha, S.; Pandian, G, N.; Sato, S.; Taniguchi, J.; Anandhakumar, C.; Hashiya, K.; Bando, T.; Sugiyama, H.
  • Journal Title: Chemistry & Biology (Cell Press) Volume: 23 Pages: 1370-1380
  • DOI: 10.1016/j.chembiol.2014.07.019
  • NAID: 120005512270
  • Peer Reviewed
• [Journal Article] Structure Evaluation of Tandem Hairpin Pyrrole-Imidazole Polyamides Recoginzing Human Telomeres. (2014)
  • Author(s): Akiyoshi Hirata, Kiyoshi Nokihara, Yusuke Kawamoto, Toshikazu Bando, Asuka Sasaki, Satoru Ide, Kazuhiro Maeshima, Takeshi Kasama, and Hiroshi Sugiyama
  • Journal Title: J. Am. Chem. Soc. Volume: 136 Pages: 11546-11554
  • DOI: 10.1021/ja506058e
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation. (2014)
  • Author(s): Patel, S.; Jung, D.; Yin, P.; Carlton, P.; Yamamoto, M.; Bando, T.; Sugiyama, H.; Lee, K, B.
  • Journal Title: ACS Nano. Volume: 8 Pages: 8959-8967
  • DOI: 10.1021/nn501589f
  • Peer Reviewed
• [Journal Article] Next-generation sequencing studies guide the design of pyrrole-imidazole polyamides with improved binding specificity by the addition of β-alanine. (2014)
  • Author(s): Anandhakumar, C.; Li, Y.; Kizaki, S.; Pandian, G. N.; Hashiya, K.; Bando, T.; Sugiyama, H.
  • Journal Title: ChemBioChem. Volume: 15 Pages: 2647-2651
  • DOI: 10.1002/cbic.201402497
  • NAID: 120005661556
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of a small molecule that turns `ON` the pluripotency gene circuitry in human fibroblasts (2014)
  • Author(s): Pandian, G, N.; Sato, S.; Anandhakumar, C.; Taniguchi, J.; Takashima, K.; Syed, J; Han, L.; Saha, A.; Bando, T.; Nagase, H.; Sugiyama, H.
  • Journal Title: ACS Chemical Biology Volume: 9 Pages: 2729-2736
  • DOI: 10.1021/cb500724t
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sequence-Specific DNA Recognition by Dimerized Cysteine Cyclic Pyrrole-Imidazole Polyamides (2014)
  • Author(s): Yamamoto, M.; Bando, T.; Morinaga, N.; Kawamoto, Y.; Hashiya, K.; Sugiyama, H.
  • Journal Title: Chem. Eur. J. Volume: 20 Pages: 752-759
  • DOI: 10.1002/chem.201302482
  • Peer Reviewed
• [Journal Article] Sequence-specific DNA Alkylation Targeting for Kras Codon 13 Mutation by Pyrrole-Imidazole Polyamide Seco-CBI Conjugates (2014)
  • Author(s): Taylor RD, Asamitsu S, Takenaka T, Yamamoto M, Hashiya K, Kawamoto Y, Bando T, Nagase H, Sugiyama H
  • Journal Title: Chem. Eur. J. Volume: 20 Pages: 1310-1317
  • DOI: 10.1002/chem.201303295
  • Peer Reviewed
• [Journal Article] Distinct DNA-based epigenetic switches trigger transcriptional activation of (2014)
  • Author(s): Pandian GN, Nagase H
  • Journal Title: Sci. Rep. Volume: 4 Pages: 3843-3843
  • DOI: 10.1038/srep03843
  • Peer Reviewed
• [Journal Article] Sequence-specific Electron Injection into DNA from an Intermolecular Electron Donor (2013)
  • Author(s): Morinaga H, Takenaka T, Hashiya F, Kizaki S, Hashiya K, Toshikazu B, Sugiyama H.
  • Journal Title: Nucleic Acids Res. Volume: (印刷中) Pages: 4724-4728
  • DOI: 10.1093/nar/gkt123
  • NAID: 120005245128
  • Peer Reviewed
• [Journal Article] Synthesis and Biological Evaluation of a Targeted DNA-Binding Transcriptional Activator with HDAC8 Inhibitory Activity (2013)
  • Author(s): Saha, A.; Pandian, G. N.; Sato, S.; Taniguchi, J.; Hashiya, K.; Bando, T.;Sugiyama, H.
  • Journal Title: Bioorg. Med. Chem. Volume: 21 Pages: 4201-4209
  • DOI: 10.1016/j.bmc.2013.05.002
  • Peer Reviewed
• [Journal Article] Effect of single pyrrole replacement with β-alanine on DNA binding affinity and sequence specificity of hairpin pyrrole/imidazole polyamides targeting 5’-GCGC-3’ (2013)
  • Author(s): Han, Y-W.; Kashiwazaki, G.; Morinaga, H.; Matsumoto, T.; Hashiya, K.; Bando, T.; Sugiyama, H.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 21 Pages: 5436-5441
  • DOI: 10.1016/j.bmc.2013.06.005
  • NAID: 120005323007
  • Peer Reviewed
• [Journal Article] A synthetic small molecule for targeted transcriptional activation of germ cell genes in a human somatic cell (2013)
  • Author(s): Han L, Pandian GN, Junetha S, Sato S, Anandhakumar C, Taniguchi J, Saha A, Bando T, Nagase H and Sugiyama H.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 52 Pages: 13410-13413
  • DOI: 10.1002/anie.201306766
  • Peer Reviewed
• [Journal Article] Development of a New Method for Synthesis of Tandem Hairpin Pyrrole-Imidazole Polyamide Probes Targeting Human Telomeres (2013)
  • Author(s): Yusuke Kawamoto, Toshikazu Bando, Fukumi Kamada, Yue Li, Kaori Hashiya, Kazuhiro Maeshima, and Hiroshi Sugiyama
  • Journal Title: J. Am. Chem. Soc. Volume: 135 Pages: 16468-16477
  • DOI: 10.1021/ja406737n
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Synthetic Small Molecule for Rapid Induction of Multiple Pluripotency Genes in Mouse Embryonic Fibroblast. (2012)
  • Author(s): Pandian GN, Nakano Y, Sato S, Morinaga H, Bando T, Nagase H, Sugiyama H
  • Journal Title: Scientific Reports Volume: 2:544 Pages: 544-544
  • DOI: 10.1038/srep00544
  • NAID: 120004770225
  • Peer Reviewed
• [Journal Article] Sequence-Selective Single-Molecule Alkylation with a Pyrrole- Imidazole Polyamide Visualized in a DNA Nanoscaffold (2012)
  • Author(s): T. Yoshidome, M. Endo, G. Kashiwazaki, K. Hidaka, T. Bando, H. Sugiyama
  • Journal Title: J. Am. Chem. Soc. Volume: 134 Pages: 4654-4660
  • DOI: 10.1021/ja209023u
  • Peer Reviewed
• [Journal Article] Synthesis of Pyrrole-Imidazole Polyamide seco-1-Chloromethyl-5-hydroxy-1, 2-dihydro-3H-benz[e]indole Conjugates with a Vinyl Linker Recognizing a 7 bp DNA Sequence (2012)
  • Author(s): Takagaki, T.; Bando, T.; Sugiyama, H.
  • Journal Title: J. Am. Chem. Soc Volume: 135 Pages: 13074-13081
  • DOI: 10.1021/ja3044294
  • Peer Reviewed
• [Presentation] 特定遺伝子の発現を制御するPI-ポリアミドの開発 (2015)
  • Author(s): 板東俊和
  • Organizer: 日本薬学会第135年会 シンポジウム：中分子創薬研究のフロンティア
  • Place of Presentation: 神戸学院大学
  • Year and Date: 2015-03-28
• [Presentation] ヒトテロメア配列に特異的に結合するタンデム型ピロール・イミダゾールポリアミドの合成 (2013)
  • Author(s): 河本佑介, 板東俊和, et al
  • Organizer: 日本化学会第93春季年会(2013)
  • Place of Presentation: 立命館大学びわこくさつキャンパス
  • Year and Date: 2013-03-25
• [Presentation] DNA塩基配列特異性を有する機能性Py-Imポリアミドの開発 (2013)
  • Author(s): 板東俊和
  • Organizer: 第２３回アンチセンスシンポジウム
  • Place of Presentation: 徳島大学
• [Remarks] 京都大学大学院理学研究科 化学専攻 生物化学分科
  • URL: http://kuchem.kyoto-u.ac.jp/chembio/
• [Remarks] 京都大学大学院理学研究科 化学専攻 生物化学分科
  • URL: http://kuchem.kyoto-u.ac.jp/chembio/
• [Remarks]
  • URL: http://kuchem.kyoto-u.ac.jp/chembio/publication1.html
• [Patent(Industrial Property Rights)] 特定遺伝子の発現を活性化するＣＴＢ－ＰＩポリアミドコンジュゲート (2015)
  • Inventor(s): 杉山 弘, 板東俊和
  • Industrial Property Rights Holder: 京都大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-025715
  • Filing Date: 2015-02-12
  • Application Year: 2015