Development of anti HIV peptide applying multifunctional polypeptide

• Project/Area Number: 15K01319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Nakashima Hideki 聖マリアンナ医科大学, 医学部, 教授 (20192669)
• Co-Investigator(Kenkyū-buntansha): 武永 美津子 聖マリアンナ医科大学, 医学研究科, 特任教授 (10236490) ; 浅井 大輔 聖マリアンナ医科大学, 医学部, 講師 (10423485)
• Co-Investigator(Renkei-kenkyūsha): FUJII Nobutaka 京都大学, 薬学部, 名誉教授 (60109014)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 抗HIV / 抗HIVペプチド / 薬物送達 / ポリペプチド / 高分子型プロドラッグ / 人工エラスチン / 注射ゲル製剤 / 創剤 / ペプチド製剤 / DDS / 徐放 / エラスチン / 生体材料 / 注射ゲル / 生分解材料 / デポ製剤

Outline of Final Research Achievements

We have developed a sustained-release anti-HIV peptide formulation, consisting of an injectable material capable of in situ self-gelation followed by spontaneous degradation, employing recombinant elastin like polypeptides. The hydrogel systems showed different anti-HIV peptide release patterns, and hydrophobic character of hydrogel is critical for high resistance to fracture and proteolytic degradation of the hydrogel. Thus, the hydrogel system may hold the promise of tailor-made long-lasting depot systems for a variety of peptide drugs.

Research Products

• [Journal Article] In situ depot formation of anti-HIV fusion-inhibitor peptide in recombinant protein polymer hydrogel (2017)
  • Author(s): Asai, D., Kanamoto, T., Takenaga, M., and Nakashima, H.
  • Journal Title: Acta Biomater. Volume: 64 Pages: 116-125
  • DOI: 10.1016/j.actbio.2017.10.024
  • Peer Reviewed
• [Journal Article] Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2) (2017)
  • Author(s): Asai, D., Nakashima, H., and Kang, J-H.
  • Journal Title: Biomed. Adv. Volume: Editors' Picks (in July 2017) Pages: 22-22
  • Open Access
• [Journal Article] Evaluation of Biological Activity of Mastic Extracts Based on Chemotherapeutic Indices. (2017)
  • Author(s): Suzuki R, Sakagami H, Amano S, Fukuchi K, Sunaga K, Kanamoto T, Terakubo S, Nakashima H, Shirataki Y, Tomomura M, Masuda Y, Yokose S, Tomomura A, Watanabe H, Okawara M, and Matahira Y.
  • Journal Title: In Vivo Volume: 31 Issue: 4 Pages: 591-598
  • DOI: 10.21873/invivo.11099
  • Peer Reviewed
• [Journal Article] Quantitative structure-cytotoxicity relationship of newly synthesized piperic acid esters. (2017)
  • Author(s): Sakagami H, Uesawa Y, Masuda Y, Tomomura M, Yokose S, Miyashiro T, Murai J, Takao K, Kanamoto T, Terakubo S, Kagaya H, Nakashima H, and Sugita Y.
  • Journal Title: Anticancer Res Volume: 37 Issue: 11 Pages: 6161-6168
  • DOI: 10.21873/anticanres.12065
  • Peer Reviewed / Open Access
• [Journal Article] マスティック抽出画分の薬理作用 (2017)
  • Author(s): 坂上宏, 天野滋, 増田宜子, 横瀬敏志, 友村美根子, 友村明人, 鈴木龍一郎, 須永克佳, 白瀧義明, 福地邦彦, 金本大成, 寺久保繁美, 中島秀喜, 渡邉博文,大川原正喜, 又平芳春
  • Journal Title: New Food Industry Volume: 59 Pages: 67-76
  • NAID: 40021313649
• [Journal Article] Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2) (2016)
  • Author(s): Asai, D., Murata, M., Toita, R., Kawano, T., Nakashima, H., and Kang, J.H.
  • Journal Title: Amino Acids Volume: 48 Issue: 12 Pages: 2875-2880
  • DOI: 10.1007/s00726-016-2345-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chemically sulfated natural galactomannans with specific antiviral and anticoagulant activities (2016)
  • Author(s): Muschin, T., Budragchaa, D., Kanamoto, T., Nakashima, H., Ichiyama, K., Yamamoto, N., Shuqin, H., and Yoshida, T.
  • Journal Title: Int. J. Biol. Macromol. Volume: 89 Pages: 415-420
  • DOI: 10.1016/j.ijbiomac.2016.05.005
  • Peer Reviewed
• [Journal Article] Isolation and antiviral activity of water-soluble Cynomorium songaricum Rupr. polysaccharides (2016)
  • Author(s): Tuvaanjav, S., Shuqin, H., Komata, M., Ma, C., Kanamoto, T., Nakashima, H., and Yoshida, T.
  • Journal Title: J. Asian Nat. Prod. Res. Volume: 18 Issue: 2 Pages: 159-171
  • DOI: 10.1080/10286020.2015.1082547
  • Peer Reviewed
• [Journal Article] Synergism of alkaline extract of the leaves of Sasa senanensis Rehder and antiviral agents (2016)
  • Author(s): Sakagami, H., Fukuchi, K., Kanamoto, T., Terakubo, S., Nakashima, H., Natori, T., Suguro-Kitajima, M., Oizumi, H., Yasui, T., and Oizumi, T.
  • Journal Title: In Vivo Volume: 30 Pages: 421-426
  • Peer Reviewed / Open Access
• [Journal Article] Antiviral and antitumor activity of licorice root extracts (2016)
  • Author(s): Fukuchi, K., Okudaira, N., Adachi, K., Odai-Ide, R., Watanabe, S., Ohno, H., Yamamoto, M., Kanamoto, T., Terakubo, S., Nakashima, H., Uesawa, Y., Kagaya, H., and Sakagami, H.
  • Journal Title: In Vivo Volume: 30 Pages: 777-785
  • Peer Reviewed / Open Access
• [Journal Article] The first reported case of central venous catheter-related fungemia caused by Cryptococcus liquefaciens (2015)
  • Author(s): Takemura H., Ohno, H., Miura, I., Takagi, T., Ohyanagi, T., Kunishima, H., Okawara, A., Miyazaki, Y., and Nakashima, H.
  • Journal Title: J. Infect. Chemother. Volume: 21 Issue: 5 Pages: 392-394
  • DOI: 10.1016/j.jiac.2014.11.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor (2015)
  • Author(s): Takenaga, M., Yamamoto, Y., Takeuchi T., Ohta, Y., Tokura, Y., Hamaguchi, A., Asai, D., Nakashima, H., Oishi, S., and Fujii, N.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 463 Issue: 3 Pages: 222-228
  • DOI: 10.1016/j.bbrc.2015.05.029
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of a cashew nut shell liquid (CNSL)-based polymer for antibacterial activity (2015)
  • Author(s): Kanehashi, S., Masuda, R., Yokoyama, K., Kanamoto, T., Nakashima, H., and Miyakoshi, T.
  • Journal Title: J. Appl. Polym. Sci. Volume: 132 Issue: 45 Pages: 42725-42725
  • DOI: 10.1002/app.42725
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Quantitative Structure-Cytotoxicity Relationship of 3-Styryl-2H-chromenes (2015)
  • Author(s): Uesawa, Y., Sakagami, H., Ishihara, M., Kagaya, H., Kanamoto, T., Terakubo, S., Nakashima, H., Yahagi, H., Takao, K., and Sugita, Y.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 5299-5307
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Synthetic galactomannans with potent anti-HIV activity (2015)
  • Author(s): Budragchaa, D., Bai, S., Kanamoto, T., Nakashima, H., Han, S., Saito, T., and Yoshida, T.
  • Journal Title: Carbohydr. Polym. Volume: 130 Pages: 233-242
  • DOI: 10.1016/j.carbpol.2015.04.047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Quantitative Structure-Cytotoxicity Relationship of Oleoylamides (2015)
  • Author(s): Sakagami, H., Uesawa, Y., Ishihara, M., Kagaya, H., Kanamoto, T., Terakubo, S., Nakashima, H., Takao, K., and Sugita, Y.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 5341-5351
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ヒト肺胞上皮細胞 A549 の培養上清によるカルバペネム薬の不活化について (2018)
  • Author(s): 竹村弘, 岡村二如, 寺久保繁美, 嶋田甚五郎, 中島秀喜
  • Organizer: 第38回神奈川県感染症医学会
• [Presentation] 注射型抗HIVペプチドデポ製剤の開発 (2017)
  • Author(s): 浅井大輔, 金本大成, 寺久保繁美, Ashutosh Chilkoti, 武永美津子, 中島秀喜
  • Organizer: 第33回日本DDS学会学術集会
• [Presentation] The reduction of L-cystine to L-cysteine by A549 cells causes carbapenems inactivation (2017)
  • Author(s): Takemura, H., Terakubo, S., Okamura, N., Shimada, J., and Nakashima, H.
  • Organizer: ASM Microbe 2017
  • Int'l Joint Research
• [Presentation] マスティック画分の生物活性の化学療法係数に基づいた再評価 (2017)
  • Author(s): 坂上宏, 鈴木龍一郎, 天野滋, 須永克佳, 金本大成, 福地邦彦, 寺久保繁美, 白瀧義明, 増田宜子, 横瀬敏志, 友村美根子, 友村明人, 中島秀喜, 渡邉博文, 大川原正喜, 又平芳春
  • Organizer: 第136回日本薬理学会関東部会
• [Presentation] ヒト細胞培養上清のCPs不活化効果の検討－第3報－ (2016)
  • Author(s): 竹村弘、寺久保繁美、嶋田甚五郎、中島秀喜
  • Organizer: 第65回日本感染症学会東日本地方会・第63回日本化学療法学会東日本支部総会 合同学会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2016-10-26
• [Presentation] 人工エラスチンポリペプチド：破傷風トキソイドデポ製剤への最適化 (2016)
  • Author(s): 浅井大輔、福田靖、諸熊一則、山口優子、Ashutosh Chilkoti、柴山恵吾、中島秀喜
  • Organizer: 第３２回日本ＤＤＳ学会学術集会
  • Place of Presentation: グランシップ（静岡県静岡市）
  • Year and Date: 2016-06-30
• [Presentation] Carbapenem-inactivating Effects of L-cysteine Derived from A549 Cells (2016)
  • Author(s): Hiromu Takemura, Shigemi Terakubo, Ninyo Okamura, Jingoro Shimada, Hideki Nakashima
  • Organizer: ASM Microbe 2016
  • Place of Presentation: Boston Convention and Exhibition Center（Boston, MA, USA）
  • Year and Date: 2016-06-16
  • Int'l Joint Research
• [Presentation] 新規合成KSP阻害剤のヒト卵巣がんに対する抗腫瘍効果 (2016)
  • Author(s): 武永美津子、竹内智起、山本有貴、都倉享恵、新美純、濱口明美、太田有紀、浅井大輔、大石真也、中島秀喜、藤井信孝
  • Organizer: 日本薬学会第１３６年会
  • Place of Presentation: パシフィコ横浜、横浜市西区
  • Year and Date: 2016-03-26
• [Presentation] 破傷風トキソイドを用いた人工エラスチン蛋白のアジュバントとしての可能性 (2015)
  • Author(s): 福田靖、浅井大輔、山口優子、諸熊一則、Ashutosh Chilkoti、中島秀喜、柴山恵吾
  • Organizer: 第１９回日本ワクチン学会学術集会
  • Place of Presentation: 名鉄犬山ホテル、愛知県犬山市
  • Year and Date: 2015-11-14
• [Presentation] インジェクタブル人工エラスチンゲルによる抗HIVペプチドのデポ製剤化 (2015)
  • Author(s): 浅井大輔、金本大成、寺久保繁美、Ashutosh Chilkoti、武永美津子、中島秀喜
  • Organizer: 第３７回日本バイオマテリアル学会大会
  • Place of Presentation: 京都テルサ、京都市南区
  • Year and Date: 2015-11-09
• [Presentation] ヒト細胞培養上清のCPs不活化効果の検討－第2報－ (2015)
  • Author(s): 竹村弘、寺久保繁美、嶋田甚五郎、中島秀喜
  • Organizer: 第64回日本感染症学会東日本地方会学術集会
  • Place of Presentation: ロイトン札幌、北海道札幌市
  • Year and Date: 2015-07-21
• [Presentation] 3-Styryl-2H-chromenes の定量的構造-細胞傷害性相関解析 (2015)
  • Author(s): 植沢芳広、加賀谷肇、石原真理子、坂上宏、金本大成、寺久保繁美、中島秀喜、矢作秀明、高尾浩一、杉田義昭
  • Organizer: 第132回日本薬理学会関東部会
  • Place of Presentation: 明海大学浦安キャンパス、千葉県浦安市
  • Year and Date: 2015-07-04
• [Presentation] Oleoylamides 誘導体の定量的構造-細胞傷害性相関解析 (2015)
  • Author(s): 石原真理子、植沢芳広、加賀谷肇、坂上宏、金本大成、寺久保繁美、中島秀喜、高尾浩一、杉田義昭
  • Organizer: 第132回日本薬理学会関東部会
  • Place of Presentation: 明海大学浦安キャンパス、千葉県浦安市
  • Year and Date: 2015-07-04
• [Presentation] インジェクタブル人工エラスチンによる抗原デポ剤：破傷風トキソイドの徐放効果の解析 (2015)
  • Author(s): 浅井大輔、福田靖、諸熊一則、Ashutosh Chilkoti、柴山恵吾、中島秀喜
  • Organizer: 第３１回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル、東京都新宿区
  • Year and Date: 2015-07-02
• [Book] ペプチド医薬品のスクリーニング・安定化・製剤化技術, 第7章 ペプチド医薬品の製剤化技術 第２節 抗HIVペプチドのデポ製剤化 (2017)
  • Author(s): 浅井大輔, 中島秀喜
  • Total Pages: 587
  • Publisher: (株)技術情報協会
• [Book] Nanostructures for Oral Medicicne, Chapter 18 Therapeutic potential of solubilized nanolignin against oral diseases (2017)
  • Author(s): Sakagami, H., Sheng, H., Yasui, T., Fukuchi, K., Oizumi, T., Ohno, H., Yamamoto, M., Fukuda, T., Kotohda, K., Yoshida, H., Kanamoto, T., Terakubo, S., and Nakashima, H.
  • Total Pages: 1034
  • Publisher: Elsevier
  • ISBN: 9780323477208
• [Book] Biological activities and action mechanisms of licorice ingredients, Chapter 6 Applicability of licorice extracts for treatment of orral diseases, evaluated by simplified in vitro assay systems with oral cells (2017)
  • Author(s): Sakagami, H., Kato, T., Fukuchi, K., Kanamoto, T., Terakubo, S., Nakashima, H., Ohno, H., and Yamamoto, M.
  • Total Pages: 172
  • Publisher: IntechOpen
  • ISBN: 9789535131205
• [Remarks] 抗微生物薬の送達手法開発（聖マリアンナ医科大学微生物学教室）
  • URL: http://www.marianna-u.ac.jp/microbiology/office/003334.html
• [Remarks] 聖マリアンナ医科大学微生物学教室
  • URL: http://www.marianna-u.ac.jp/microbiology/