Development of Noble Structure PI Polyamide Recognizing to a Unique Sequence on double-strand DNA

• Project/Area Number: 22790301
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Nihon University
• Principal Investigator: WATANABE Takayoshi 日本大学, 理工学部・物質応用化学科, 研究員 (60526060)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: PIポリアミド / 固相合成法 / ユニーク型PIポリアミド / ポリアミドブロック / ABCA1 / 遺伝子発現抑制 / 水溶性の向上 / 環状PIポリアミド / リシンテール / PEG-HMPB-レジン / ブロックユニット

Research Abstract

Cross form PI polyamide having 0alaninelPy or p-alanine/lm was succeeded in making into a target all DNA sequence without GGGG and CCCC. Then, for the synthesis of long chain PI polyamide recognizing 12 base-pair DNA sequence, 2-3 mer PI polyamide blocks by solid phase synthesis using HMPB resin was developed and the long chain PI polyamide could be synthesized elongating these PI polyamide blocks. And it was established that solid phase synthesis of the cyclic PI polyamides more strong DNA binding than hair-pin PI polyamide.

Research Products

• [Journal Article] Transcriptional inhibition of hypertrophic scars by a gene silencer pyrrole-imidazole polyamide, targeting to the TGF-bl promoter (2011)
  • Author(s): Washio H, Fukuda N, Matsuda H, Nagase H, Watanabe T, Matsumoto Y, Terui T.
  • Journal Title: Journal of Investigative Dermatology Volume: 10 Pages: 1038-1038
  • Peer Reviewed
• [Journal Article] Transcriptional in hibition of hypertrophicscars by a gene silencer pyrroleimidazole polyamide targeted to the TGF-b 1 promoter (2011)
  • Author(s): Matsuda Y, Fukuda N, Ueno T, Katakawa M, Wang X, Watanabe T, Matsui S, Aoyama T, Saito K, Banda T, Matsumoto Y, Nagase H, Matsumoto K, Sugiyama H.
  • Journal Title: Kidney International Volume: 79(1) Pages: 46-56
  • Peer Reviewed
• [Journal Article] Development of a novel gene silencer pyrrole-imidazole polyamide targeting human connective tissue growth factor (2011)
  • Author(s): Wan JX, Fukuda N, Ueno T, Watanabe T, Matsuda H, Saito K, et al
  • Journal Title: Biol Pharm Bull Volume: 34(10) Pages: 1572-1577
  • NAID: 130001086589
  • Peer Reviewed
• [Journal Article] Transcriptional inhibition of hypertrophic scars by a gene silencer, pyrrole-imidazole polyamide, targeting the TGF-β1 promoter (2011)
  • Author(s): Washio H, Fukuda N, Matsuda H, Nagase H, Watanabe T, et al
  • Journal Title: J Invest Dermatol Volume: 131(10) Pages: 1987-1995
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of progressive renal disease by the gene silencing pyrrole-imidazole polyamide targeted to the TGF-b1 promoter. (2011)
  • Author(s): Matsuda Y, Fukuda N, Ueno T, Katakawa M, Wang X, Watanabe T, et al
  • Journal Title: Kidney International Volume: 79(1) Pages: 46-56
  • Peer Reviewed
• [Journal Article] Inhibition of MMP-g transcription and suppression of tumor metastasis by pyrroleimidazole polyamide (2010)
  • Author(s): Wang X, Nagase H, Watanabe T, Nobusue H, Suzuki T, Asami Y, Shinojima Y, Kawashima H, Takagi K, Mishra R, Igarashi J, Kimura M, Takayama T, Fukuda N, Sugiyama H.
  • Journal Title: Cancer Science Volume: 101(3)
  • Peer Reviewed
• [Journal Article] Inhibition of MMP-9 transcription and suppression of tumor metastasis by pyrrole-imidazole polyamide (2010)
  • Author(s): Wang X, Nagase H, Watanabe T, Nobusue H, Suzuki T, et al
  • Journal Title: Cancer Science Volume: 101(3) Pages: 759-766
  • NAID: 10026589912
  • Peer Reviewed
• [Journal Article] Pretranscriptional regulation of regulation of Tgf-beta1 by PI polyamide prevents scarring and accelerates wound healing of cornea after exposure to alkali (2010)
  • Author(s): Chen M, Matsuda H, Wang L, Watanabe T Kimura MT, Nagase H., et al
  • Journal Title: Molecular Therapy Volume: 18(3) Pages: 519-527
  • Peer Reviewed
• [Presentation] ゲノム上のユニーク配列を認識するための新規PIポリアミドの開発 (2010)
  • Author(s): 渡部隆義、永瀬浩喜
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] ゲノム上のユニーク配列を認識するための新規PIポリアミドの開発 (2010)
  • Author(s): 渡部隆義
  • Organizer: 分子生物学会
  • Place of Presentation: 神戸ポートアイランド2P-1315
  • Year and Date: 2010-12-08