Synthesis and inhibitory activity of cyclic depsi-peptide with anti-HIV activity

• Project/Area Number: 19790095
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KONNO Hiroyuki Kyoto Prefectural University of Medicine, 大学院・医学研究科, 助教 (50325247)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,630,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: 医薬品化学 / 合成化学 / ウイルス / 生体分子 / 生理活性 / 有機化学 / カリペルチン / 抗HIV / 異常アミノ酸

Research Abstract

カリペルチンAの固相全合成を目指し、まず予備実験を兼ねたカリペルチンBおよびカリペルチンEの固相全合成を行った。構成する異常アミノ酸の安全にかつグラムスケール合成に優れる方法を開発した。つぎに調製したFmoc-異常アミノ酸類と入手可能なFmoc-アミノ酸を用いて固相上でペプチドの伸長実験を行った。その結果、カリペルチンEならびにカリペルチンBの全合成に成功した。今後、環状化の条件検討を引き続き行いながら、アナログ体合成についても行い、CCR5とのアンタゴニスト活性の測定を行っていく。

Research Products

• [Journal Article] Total synthesis of cis-solamin A, a mono-tetrahydrofuran acetogenin isolated from Annona muricata (2008)
  • Author(s): Konno, H.; Okuno, Y.; Makabe, H.; Nosaka, K.; Onishi, A.; Abe, N.; Sugimoto, A.; Akaji, K
  • Journal Title: Tetrahedron Lett 49(5) Pages: 782-785
• [Journal Article] Possible involvement of thiaminase II encoded bythe THI20 gene in thiamine salvage ofSaccharomyces cerevisiae (2008)
  • Author(s): Onozuka, M.; Konno, H.; Kawasaki, Y.; Akaji, K.; Nosaka, K
  • Journal Title: J. FEMS Yeast Research 8(2) Pages: 266-275
• [Journal Article] Synthesis of Pyranicin and its Inhibitory Action with Bovine Heart Mitochondrial Complex (2008)
  • Author(s): Hattori, N.; Furuhata, S.; Okajima, M.; Konno, H.; Abe, M.; Miyoshi, H.; Goto, T, Makabe, H
  • Journal Title: I. Org. Lett 10(5) Pages: 717-720
• [Journal Article] Total synthesis of pyranicin and its deoxygenated analogues and their inhibitory action with bovine heart mitochondrial complex (2008)
  • Author(s): Furuhata, S.; Hattori, Y.; Okajima, M.; Konno, H.; Abe, M.; Miyoshi, H.; Goto, T.; Makabe, H
  • Journal Title: I. Tetrahedron 64 Pages: 7695-7703
• [Journal Article] Evaluation of Lipid-Binding Propaties of the N-Terminal Helical Segments in Human Apolipoprotein A-I Using Fragment Peptides (2008)
  • Author(s): Tanaka, M.; Tanaka, T.; Ohta, S.; Kawakami, T.; Konno, H.; Akaji, K.; Aimoto, S.; Saito, H
  • Journal Title: J. Peptide Sci 15(1) Pages: 36-42
• [Journal Article] Thiamin-dependent transactivation activity of PDC2 in Saccharomyces (2008)
  • Author(s): Nosaka, K.; Onozuka, M.; Konno, H.; Akaji, K
  • Journal Title: FEBS Lett 582(29) Pages: 3991-3996
• [Journal Article] Evaluation of Peptide Aldehyde Inhibitors using R188I Mutant of SARS 3CL Protease as aproteolysis-resistant mutant (2008)
  • Author(s): Akaji, K.; Konno, H.; Onozuka, M.; Makino, A.; Nosaka, K
  • Journal Title: Bioorg. Med. Chem 16 Pages: 9400-9408
• [Journal Article] Evaluation of Peptide Aldehyde Inhibitors using R1881 Mutant of SARS 3CL Protease as a proteolysi (2008)
  • Author(s): Akaji, K. ; Konno, H. ; Onozuka, M. ; Mak
  • Journal Title: Bioorg. Med. Chem. 16 Pages: 9400-9408
  • Peer Reviewed
• [Journal Article] Thiamin-dependent transactivation activity of PDC2 in Saccharomyces (2008)
  • Author(s): Nosaka, K. ; Onozuka, M. ; Konno, H. ; Al
  • Journal Title: FEBS Lett. 582 Pages: 3991-3996
  • Peer Reviewed
• [Journal Article] Total synthesis of cis-solamin A, a mono-tetrahydrofuran acetogenin isolated from Annona muricata (2008)
  • Author(s): Konno, H. ; Okuno, Y. ; Makabe, H. ; Nos
  • Journal Title: Tetrahedron Lett. 49 Pages: 782-785
  • Peer Reviewed
• [Journal Article] Synthesis of (17S, 18S)-and (17R, 18R)-tonkinelin and their inhibitory action with bovine heart mitochondorial complex (2007)
  • Author(s): Hattori, Y.; Konno, H.; Abe, M.; Miyoshi, H.; Goto, T.; Makabe, H.
  • Journal Title: I. Bioorg. Med. Chem 15 Pages: 3026-3031
• [Journal Article] Studies on Substrate Specificity at PR/p3 Cleavage Site of HTVL-1 Protease (2007)
  • Author(s): Bang, J. K.; Teruya, K.; Aimoto, S.; Konno, H.; Nosaka, K.; Tatsumi, T.; Akaji, K.
  • Journal Title: Int. J. Peptide Res. 13 Pages: 173-179
• [Journal Article] Synthesis of Miraziridine A and Identification of Its Major Reactive Site for Cathepsin (2007)
  • Author(s): Konno, H.; Kubo, K.; Makabe, H.; Toshiro, E.; Nosaka, K.; Akaji, K. Total
  • Journal Title: B. Tetrahedron 63(38) Pages: 9502-9513
• [Journal Article] Synthesis of All Stereoisomers of β-Methoxy Tyrosine Derivatives and Identification of the Absolute Configration in Callipeltin (2007)
  • Author(s): Konno, H.; Aoyama, S.; Nosaka, K.; Akaji, K
  • Journal Title: E, Synthesis (23) Pages: 3666-3672
• [Journal Article] Synthesis,determination of the absolute configuration of tonkinelin and inhibitory action with bovine heart mitochondrial complex I (2007)
  • Author(s): Hattori, Y.; Konno, H.; Abe, M.; Miyoshi, H.; Goto, T; Makabe, H.
  • Journal Title: Bioorg.Med.Chem 15 Pages: 3026-3031
  • Peer Reviewed
• [Journal Article] Total synthesis of miraziridine A and identification of major reaction site for cathepsin B (2007)
  • Author(s): Konno, H.; Kubo, K.; Makabe, H.; Toshiro, E.; Hinoda, N.; Nosaka, K.; Akaji, K
  • Journal Title: Tetrahedron 63(38) Pages: 9502-9513
  • Peer Reviewed
• [Journal Article] Stereoselective Synthesis of All Stereoisomers of β-Methoxy Tyrosine Derivatives for Identification of the Absolute Configuration in Callipeltin E (2007)
  • Author(s): Konno, H.; Aoyama, S.; Nosaka, K; Akaji, K
  • Journal Title: Synthesis 23 Pages: 3666-3672
  • Peer Reviewed
• [Presentation] レトロインベルソペプチド型HTLV-1プロテアーゼ阻害剤の合成と構造活性相関 (2008)
  • Author(s): 粟原千如、辰巳正、今野博行、野坂和人、赤路健一
  • Organizer: 第34回反応と合成の進歩シンポジウム
  • Place of Presentation: 京都市、京都テルサ
  • Year and Date: 2008-11-04
• [Presentation] Synthestic Studies on Callipeltins B and E isolated form marine sponge (2008)
  • Author(s): 今野博行、野坂和人、赤路健一
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 東京都、船堀タワーホール
  • Year and Date: 2008-10-29
• [Presentation] Synthestic Studies on Callipeltins B and E isolated form marine sponge (2008)
  • Author(s): 今野博行、野坂和人、赤路健一
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 東京、船堀タワーホール
  • Year and Date: 2008-10-29
• [Presentation] Syntheses and Evaluations of Peptide based Inhibitors for R188I Mutant of SARS 3CL protease (2008)
  • Author(s): 三井寛法、高橋真矢子、今野博行、野坂和人、赤路健一
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 東京都、船堀タワーホール
  • Year and Date: 2008-10-28
• [Presentation] レトロインベルソペプチド型HTLV-1プロテアーゼ阻害剤の合成 (2008)
  • Author(s): 粟原千如、辰巳正、今野博行、野坂和人、赤路健一
  • Organizer: 日本薬学会年会、2008年度大会要旨集2
  • Place of Presentation: 横浜市、パシフィコ横浜
  • Year and Date: 2008-03-29
• [Presentation] 変異型SARS3CLproteaseを用いた新規アルデヒド型阻害剤の評価 (2008)
  • Author(s): 高橋麻矢子、野坂和人、今野博行、赤路健一
  • Organizer: 日本薬学会年会、2008年度大会要旨集2
  • Place of Presentation: 横浜市、パシフィコ横浜
  • Year and Date: 2008-03-29
• [Presentation] ミトコンドリアComplexIを阻害するアセトゲニンcis-solamin-Aの合成と阻害能に関する研究 (2008)
  • Author(s): 今野博行、奥野康弘、真壁秀文、野坂和人、赤路健一
  • Organizer: 日本薬学会年会、2008年度大会要旨集2
  • Place of Presentation: 横浜市、パシフィコ横浜
  • Year and Date: 2008-03-28
• [Presentation] Total Synthesis of Miraziridine A and Its Analogues. (2007)
  • Author(s): Konno, H.; Kubo, K; Makabe, H.; Nosaka, K; Akaji, K.
  • Organizer: Int. Peptides Sympodium(IPS4)
  • Place of Presentation: Cairns,Australia
  • Year and Date: 2007-10-23
• [Presentation] Synthesis and structure activity relationship Studies of iraziridine A, a cysteine protease inhibitor (2007)
  • Author(s): 今野博行、久保佳奈子、真壁秀文、野坂和人、赤路健一
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 富山市、富山コンベンションセンター
• [Presentation] Evaluation of peptide-based inhibitors using R188I mutant of SARS 3CL protease as aproteolysis-resistant mutant (2007)
  • Author(s): 赤路健一、今野博行、小野塚真理、齋藤裕行、牧野歩、野坂和人
  • Organizer: 第45回ペプチド討論会
  • Place of Presentation: 富山市、富山コンベンションセンター
• [Presentation] レトロインベルソペプチド型HTLV-1プロテアーゼ阻害剤の合成と構造活性相関 (2007)
  • Author(s): 辰巳正、粟原千如、仲裕美、相本三郎、今野博行、野坂和人、赤路健一
  • Organizer: メディシナルケミストリーシンポジウム
  • Place of Presentation: 相模原市、相模原文化センター
• [Presentation] ブリックホール (2006)
  • Author(s): 今野博行、久保佳奈子、真壁秀文、野坂和人、赤路健一
  • Organizer: 第33回反応と合成の進歩シンポジウム
  • Place of Presentation: 長崎市
• [Remarks]
  • URL: http://www.f.kpu-m.ac.jp/y/chem/index.html