1992 Fiscal Year Annual Research Report

新規構造を有する天然物由来抗癌物質に関する研究

Research Project

Project/Area Number	04151016
Research Institution	The University of Tokyo
Principal Investigator	瀬戸治男東京大学, 応用微生物研究所, 教授 (10013335)
Co-Investigator(Kenkyū-buntansha)	吉田稔東京大学, 農学部, 助手 (80191617) 馬替純二東工大学, 生命理工学部, 講師 (60199643) 長田裕之理化学研究所, 主任研究員 (80160836) 長尾善光徳島大学, 薬学部, 教授 (40027074) 岩崎成夫東京大学, 応用微生物研究所, 教授 (00013326)
Keywords	JS49 / ustiloxin A / reveromycin / radicicol / gilvocarcinの化学変換 / roseophilin / 多剤耐性克服 / 抗ガン物質
Research Abstract	本年度の各班員の研究実績は以下のとおりである。(瀬戸)ハピローマウイルスでトランスフォームしたNIH3T3細胞を正常化させる物質を検索し,放線菌の培養液から新規化合物であるJS49を単離し、その構造を決定した。また放線菌の培養液から強い細胞障害性を示す新規マクロライドを単離した。(岩崎)イネ病稲こうじより単離したustiloxin Aの構造を確定し、13員環構造を含む環状ペプチドであることを明らかにした。本化合物は既知化合物中、最強のチューブリン重合阻害活性を示した。(長田)reveromycin Aのラベル体を作成し、予備的検討により真核細胞の細胞質にreveromycinAと結合する蛋白質が存在することを示した。(吉田)フローサイトメーターによる細胞DNA含量の直接定量を用いた検索の結果、トランスフォームした細胞の細胞周期をG1、G2期で停止させるとともにその形態を正常化させる物質としてradicicolを再発見した。(馬替)脾臓細胞の幼若化反応を用いた探索系においてT細胞の幼若化を特異的に抑制する物質としてleucanicidinを同定した。またroseophilinがConAとの相乗効果を示し、細胞内小器官の酸性化を阻害することを見いだした。(長尾)campthotecinの誘導体を合成し、P388担癌マウスでの延命効果を検討したところ、ジヒドロキシクロトン酸エステルに抗癌活性が認められた。(柿沼)gilvocar Vから誘導したヒドロキシメチルギルボカルシンテトラアセタートを用いて、グリコシル体を調製した。(内藤)動植物細胞から酵母に至るまですべての細胞に存在するユビキチン系における作用点は、cisplatinとaclarubisinとでは異なり、cisplatinはタンパク質へのユビキチンの結合過程を阻害し、一方aclarubicinはユビキチン化タンパク質の分解過程を阻害することが明らかになった。

Research Products

(24 results)

All Other

All Publications (24 results)

[Publications] Y.Hayakawa: "Structure of a new antibiotic,roseophilin." Tetrahedron Lett.33. 2701-2704 (1992)
[Publications] M.Nakagawa: "Studies on viridenomycin,a novel 24-membered macrocyclic lactam antibiotic." J.Antibiotics. 45. 1133-1138 (1992)
[Publications] S.Imai: "Exfoliazone and lavanducyanin,Potent growth promoting substances of rat liver cell line,RLN-8,produced by Streptomyces exfoliatusand Streptomyces aeriouvifer." J.Antibiotics. 46. (1993)
[Publications] S.Imai: "Resorcinin,a mammalian cell growth stimulating substance produced by Cytophaga Johnsonae." J.Antibiotics. 46. (1993)
[Publications] M.Nakai: "Studies on a microbial metabolite,trichostatin D,inducing morphological reversion of transformed cells." J.Antibiotics. 46. (1993)
[Publications] Y.Li: "Interaction of phomopsin a with porcine brain tubulin.Inhibition of tubulin polymerzation and binding at a rhizoxin binding site." Biochem.Pharmacol.43. 219-224 (1992)
[Publications] Y.Koiso: "Ustiloxin:A phytotoxin and mycotoxin from false smut balls on rice panicles." Tetrahedron Lett.33. 4157-4160 (1992)
[Publications] Y.Li: "Binding selectivity of rhizoxin,phomopsin A,vinblastinen,and ansamitocin P-3 to fungal tubulin:differential interactions of these antibiotic agents with brain and fungal tubulins." Biochem.Biophys.Res.Commun.187. 722-729 (1992)
[Publications] T.Sawada: "Identification of the fragment photoaffinity-labeled with azidodansyl-rhizoxin as Met-363 Lys-379 on tubulin." Biochem.Pharmacol.(1993)
[Publications] H.Osada: "Epiderstatin induces the flat reversion of NRK cells transformed by temperature-sensitive Rouse sarcoma virus." Biosci.Biotech.Biochem.56. 1801-1806 (1992)
[Publications] H.Takahashi: "Reveromycins,new inhibitors of eukaryotic cell growth.I.Producing organism,fermentation,isolation and physico-chemical properties." J.Antibiotics. 45. 1409-1413 (1992)
[Publications] H.Takahashi: "Reveromycins,new inhibitors of eukaryotic cell growth.II.Biological activities." J.Antibiotics. 45. 1414-1419 (1992)
[Publications] H.Koshino: "Reveromycins,new inhibitors of eukaryotic cell growth.III.Structures." J.Antibiotics. 45. 1420-1427 (1992)
[Publications] H.Sasaki: "Leptomycin B-induced fixation of X-ray-related potentially lethal damage." Radiat.Res.129. 163-170 (1992)
[Publications] K.Nishi: "A leptomycin B resistance gene of Schizosaccharomyces pombe encodes a protein similar to the mammalian P-glycoproteins." Mol.Microbiol.6. 761-769 (1992)
[Publications] H.J.Kwon: "Radicicol,an agent inducing the reversal of transforned phenotypes of src-transformed fibrodlasts." Biosci.Biotech.Biochem.56. 538-539 (1992)
[Publications] H.J.Kwon: "Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol." Cancer Res.52. 6926-6930 (1992)
[Publications] K.Abe: "Leptolstatin from <Streptomyces>___- sp.SAM1595,a new gap phase-specific inhibitor of the mammalian cell cycle.I.Screening,taxonomy,purification and biological activities." J.Antibiotics. 46. (1993)
[Publications] T.Kataoka: "Effects of prodigiosin 25-C on cultured cell lines:its similarity to monovalent polyether ionophores and vacuolar type H^+-ATPase inhibitors." J.Antibiotics. 45. 1618-1625 (1992)
[Publications] J.Magae: "Effect of microbial products on glucose consumption and morphology of macrophages." Biosci.Biotech.Biochem.(1993)
[Publications] M.Naito: "Reversal of multidrug resistance by an immunosuppressive agent FK-506." Cancer Chemother.Pharmacol.29. 195-200 (1992)
[Publications] T.Isoe: "Inhibition of different steps of the ubiquitin system by cisplatin and aclarubucin." Biochim.Biophys.Acta. 1117. 131-135 (1992)
[Publications] M.Naito: "Functionally active homodimer of P-glycoprotein in multidrug-resistant tumor cells." Biochem.Biophys.Res.Commun.185. 284-290 (1992)
[Publications] T.Tatsuta: "Functional involvement of P-glycoprotein in blood-brain barrier." J.Biol.Chem.267. 20383-20391 (1992)

1992 Fiscal Year Annual Research Report

新規構造を有する天然物由来抗癌物質に関する研究

Principal Investigator

瀬戸 治男 東京大学, 応用微生物研究所, 教授 (10013335)

Research Products

[Publications] Y.Hayakawa: "Structure of a new antibiotic,roseophilin." Tetrahedron Lett.33. 2701-2704 (1992)

[Publications] M.Nakagawa: "Studies on viridenomycin,a novel 24-membered macrocyclic lactam antibiotic." J.Antibiotics. 45. 1133-1138 (1992)

[Publications] S.Imai: "Exfoliazone and lavanducyanin,Potent growth promoting substances of rat liver cell line,RLN-8,produced by Streptomyces exfoliatusand Streptomyces aeriouvifer." J.Antibiotics. 46. (1993)

[Publications] S.Imai: "Resorcinin,a mammalian cell growth stimulating substance produced by Cytophaga Johnsonae." J.Antibiotics. 46. (1993)

[Publications] M.Nakai: "Studies on a microbial metabolite,trichostatin D,inducing morphological reversion of transformed cells." J.Antibiotics. 46. (1993)

[Publications] Y.Li: "Interaction of phomopsin a with porcine brain tubulin.Inhibition of tubulin polymerzation and binding at a rhizoxin binding site." Biochem.Pharmacol.43. 219-224 (1992)

[Publications] Y.Koiso: "Ustiloxin:A phytotoxin and mycotoxin from false smut balls on rice panicles." Tetrahedron Lett.33. 4157-4160 (1992)

[Publications] Y.Li: "Binding selectivity of rhizoxin,phomopsin A,vinblastinen,and ansamitocin P-3 to fungal tubulin:differential interactions of these antibiotic agents with brain and fungal tubulins." Biochem.Biophys.Res.Commun.187. 722-729 (1992)

[Publications] T.Sawada: "Identification of the fragment photoaffinity-labeled with azidodansyl-rhizoxin as Met-363 Lys-379 on tubulin." Biochem.Pharmacol.(1993)

[Publications] H.Osada: "Epiderstatin induces the flat reversion of NRK cells transformed by temperature-sensitive Rouse sarcoma virus." Biosci.Biotech.Biochem.56. 1801-1806 (1992)

[Publications] H.Takahashi: "Reveromycins,new inhibitors of eukaryotic cell growth.I.Producing organism,fermentation,isolation and physico-chemical properties." J.Antibiotics. 45. 1409-1413 (1992)

[Publications] H.Takahashi: "Reveromycins,new inhibitors of eukaryotic cell growth.II.Biological activities." J.Antibiotics. 45. 1414-1419 (1992)

[Publications] H.Koshino: "Reveromycins,new inhibitors of eukaryotic cell growth.III.Structures." J.Antibiotics. 45. 1420-1427 (1992)

[Publications] H.Sasaki: "Leptomycin B-induced fixation of X-ray-related potentially lethal damage." Radiat.Res.129. 163-170 (1992)

[Publications] K.Nishi: "A leptomycin B resistance gene of Schizosaccharomyces pombe encodes a protein similar to the mammalian P-glycoproteins." Mol.Microbiol.6. 761-769 (1992)

[Publications] H.J.Kwon: "Radicicol,an agent inducing the reversal of transforned phenotypes of src-transformed fibrodlasts." Biosci.Biotech.Biochem.56. 538-539 (1992)

[Publications] H.J.Kwon: "Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol." Cancer Res.52. 6926-6930 (1992)

[Publications] K.Abe: "Leptolstatin from <Streptomyces>___- sp.SAM1595,a new gap phase-specific inhibitor of the mammalian cell cycle.I.Screening,taxonomy,purification and biological activities." J.Antibiotics. 46. (1993)

[Publications] T.Kataoka: "Effects of prodigiosin 25-C on cultured cell lines:its similarity to monovalent polyether ionophores and vacuolar type H^+-ATPase inhibitors." J.Antibiotics. 45. 1618-1625 (1992)

[Publications] J.Magae: "Effect of microbial products on glucose consumption and morphology of macrophages." Biosci.Biotech.Biochem.(1993)

[Publications] M.Naito: "Reversal of multidrug resistance by an immunosuppressive agent FK-506." Cancer Chemother.Pharmacol.29. 195-200 (1992)

[Publications] T.Isoe: "Inhibition of different steps of the ubiquitin system by cisplatin and aclarubucin." Biochim.Biophys.Acta. 1117. 131-135 (1992)

[Publications] M.Naito: "Functionally active homodimer of P-glycoprotein in multidrug-resistant tumor cells." Biochem.Biophys.Res.Commun.185. 284-290 (1992)

[Publications] T.Tatsuta: "Functional involvement of P-glycoprotein in blood-brain barrier." J.Biol.Chem.267. 20383-20391 (1992)

瀬戸治男東京大学, 応用微生物研究所, 教授 (10013335)