Development of a method to induce apoptosis by HIV locked in a cell
Project/Area Number |
17K08861
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Virology
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Research Institution | Kumamoto University |
Principal Investigator |
Fujita Mikako 熊本大学, 大学院生命科学研究部(薬), 特任教授 (00322256)
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Co-Investigator(Kenkyū-buntansha) |
大塚 雅巳 熊本大学, 大学院生命科学研究部(薬), 客員教授 (40126008)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | エイズ完治 / HIV / 潜伏感染細胞 / イノシトールリン脂質 / アポトーシス / プロドラッグ体 / X線結晶解析 / フィチン酸 / 誘導体 / エイズ根治 / Gag / MA / X線構造解析 / IP6 / HIV根絶 / HIV放出抑制 / DSFアッセイ / 細胞内導入キャリア / ウイルス / 感染症 / 薬学 / 脂質 |
Outline of Final Research Achievements |
The biggest goal of remedy of AIDS at the moment is removal of HIV reservoir from the patients, that is cure. We already developed an inhibitor of HIV release named L-HIPPO. It was further found that this compound causes accumulation of HIV proteins causing cellular death, and we named this phenomenon “lock-in and apoptosis”. This would lead to cure of AIDS in near future. Herein we tried to improve this method. For example, we synthesized prodrug of L-HIPPO to carry a highly negatively charged compound inside of a cell. It is under the final purification now. X-ray crystallographic study of IP6, a part of L-HIPPO, and its target protein MA was also performed to understand how L-HIPPO interacts with the MA.
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Academic Significance and Societal Importance of the Research Achievements |
現在、世界では3000万人以上のHIV感染者がいることが知られる。適切に抗HIV剤が投与されていれば、彼らは健常人とほぼ同じように生活することができる。しかし、HIV潜伏感染細胞は残ったままで、抗HIV剤の投与を中断するとHIVはすぐに体内で増える。本研究を発展させれば、このHIV潜伏感染細胞を感染者体内から除去することに繋がるはずである。この「ウイルスを細胞内に閉じ込めて細胞を殺す」という概念は新しく、HIVのみならず様々な抗ウイルス戦略に応用できるはずである。また、L-HIPPOのような非天然型イノシトールリン脂質誘導体を薬に発展させるという考え方も新しい。
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] New SIRT2 inhibitors: Histidine-based bleomycin spin-off2019
Author(s)
Ali Taha F.S.、Ciftci Halil I.、Radwan Mohamed O.、Koga Ryoko、Ohsugi Takeo、Okiyama Yoshio、Honma Teruki、Nakata Akiko、Ito Akihiro、Yoshida Minoru、Fujita Mikako、Otsuka Masami
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Journal Title
Bioorganic & Medicinal Chemistry
Volume: 27
Issue: 9
Pages: 1767-1775
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Design, synthesis and biological evaluation of novel 1,3,4-Thiadiazole derivatives as potential antitumor agents against chronic myelogenous leukemia. Striking effect of nitrothiazole moiety.2018
Author(s)
Altintop, M.D., Ciftci, H.I., Radwan, M.O., Sever, B., Kaplancikli, Z.A., Ali, T.F.S., Koga, R., Fujita, M., Otsuka, M., and Ozdemir, A.
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Journal Title
Molecules
Volume: 23
Issue: 1
Pages: 59-59
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The First Pentacyclic Triterpenoid Gypsogenin Derivative Exhibiting Anti-ABL1 Kinase and Anti-chronic Myelogenous Leukemia Activities2018
Author(s)
Ciftci, H.I., Ozturk, S.E., Ali, T.F.S., Radwan, M.O., Tateishi, H., Koga, R., Ocak, Z., Can, M., Otsuka, M., and Fujita, M.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 41
Issue: 4
Pages: 570-574
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A novel inhibitor of farnesyltransferase with a zinc site recognition moiety and a farnesyl group.2017
Author(s)
Tanaka, A., Radwan, M.O., Hamasaki, A., Ejima, A., Obata, E., Koga, R., Tateishi, H., Okamoto, Y., Fujita, M., Nakao, M., Umezawa, K., Tamanoi, F., and Otsuka, M.
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Journal Title
Bioorganic & Medicinal Chemistry Letters
Volume: 27
Issue: 16
Pages: 3862-3866
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”.2017
Author(s)
Tateishi, H., Monde, K., Anraku, K., Koga, R., Hayashi, Y., Ciftci, H.I., DeMirci, H., Higashi, T., Motoyama, K, Arima, H., Otsuka, M., and Fujita, M.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 8957-8957
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A dithiol compound binds to the zinc finger protein TRAF6 and suppresses its ubiquitination.2017
Author(s)
Koga, R., Radwan, M.O., Ejima, T., Kanemaru, Y., Tateishi, H., Ali, T.F.S., Ciftci, H.I., Shibata, Y., Taguchi, Y., Inoue, J., Otsuka, M., and Fujita, M.
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Journal Title
ChemMedChem
Volume: 12
Issue: 23
Pages: 1935-1941
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] TRAF6 polyubiquitination interruption by a low molecular weight zinc chelator2017
Author(s)
Mohamed O. Radwan, Ryoko Koga, Tomohiko Ejima, Yosuke Kanemaru, Hiroshi Tateishi, Taha F. S. Ali, Halil Il Ciftci, Yuri Shibata, Yuu Taguchi, Jun-ichiro Inoue, Masami Otsuka, Mikako Fujita
Organizer
第35回メディシナルケミストリーシンポジウム
Related Report
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