1990 Fiscal Year Annual Research Report

細胞表層の精密構造認識と機能性制御

Research Project

Project/Area Number	02250106
Research Institution	Kyoto University
Principal Investigator	砂本順三京都大学, 工学部, 教授 (80037811)
Co-Investigator(Kenkyū-buntansha)	久枝良雄九州大学, 工学部, 助教授 (70150498) 横山茂之東京大学, 理学部, 助教授 (00159229) 猪飼篤東京工業大学, 理学部, 教授 (50011713) 竹市雅俊京都大学, 理学部, 教授 (00025454)
Keywords	ガングリオシド / ガドヘレン / αー2ーマクログロブリン / ヒト上皮成長因子 / シクロファン / リポソ-ム / 動物細胞 / ペプチド
Research Abstract	細胞間接着、細胞間情報伝達、あるいは細胞膜を介しての細胞内への情報伝達などにおいては、細胞表層で起こる抗原ー抗体反応や、リガンドーレセプタ-結合による精密な分子認識が行われている。本研究班においては、細胞表層に存在している各種の認識素子、例えば糖脂質、糖蛋白質の糖鎖、レセプタ-蛋白質のシグナル結合部位、あるいは抗体や抗原分子の関与する認識メカニズムを精密構造レベルで追求し、実細胞間の情報伝達メカニズムを理解する。さらに得られた情報を基に精密構造認識に続く細胞機能の制御の可能性を探る。これまでに得られた研究成果を以下にまとめた。 1.牛脳から単離したガングリオシドを組込んだリポソ-ムにより血清中に誘起される抗体産生能は、モノシアロガングリオシドよりもポリシアロガングリオシドの方が高いことを見い出し、メラノ-マにたいするリポソ-ムワクチンの作成に初めて成功した(砂本)。 2.ヒト上皮成長因子(hEGF)と細胞表層レセプタ-とのシグナル伝達メカニズムを分子レベルで解析するために、蛍光プロ-ブを組み込んだhEGF変異体を蛋白質工学により合成した(横山)。 3.蛋白質酵素捕獲因子であるα2ーマクログロブリン(α2ーM)はプロテア-ゼと結合することにより、細胞表層にある受容体に対する特異的結合部位を露出する。細胞表層へのα2ーMの結合メカニズムの解析に先だって、走査型トンネル顕微鏡(STM)の試作を行なった(猪飼)。 4.細胞間接着においては、カドヘリンと非共有結合で相互作用している細胞内ドメインが必要であり、またC端を欠失したカドヘリン分子は細胞内骨格との結合性を失って細胞間境界に濃縮されない事を見いだした。さらに発現されるカドヘリンのタイプの転換が細胞集団の形態形成制御と関連していることを見いだした(竹市)。 5.細胞表面でのレセプタ-の精密分子認識モデルとして、マクロ環化合物による人工レセプタ-分子の開発を行った。シクロファン型の包接ホストにカテコ-ルを導入した新しい人工レセプタ-は、リガンドとして金属イオンと有機分子が相互作用した形で包接することを見いだした(久枝)。

Research Products

(29 results)

All Other

All Publications (29 results)

[Publications] J.Sunamoto: "Devterium Nuclear Magnetic Resonance Studies on the Interaction of Glycophorin with 1,2ーDimyristoylamidoー1,2ーdeoxyphosphatidylcholine." Biochim.Biophys.Acta. 1024. 220-226 (1990)
[Publications] K.Akiyoshi: "Cell Specificity of Polysaccharide DerivativesonLiposomdl Surface" Chem.,Lett.473-476 (1990)
[Publications] S.Shibata: "Targeting Chemotherapy of Brain Tumor Using LiposomeーEncapsolated CisplatinーPart 1.Substances Associated with Liposomes to Target Brain Tumor" D.D.S.5. 83-87 (1990)
[Publications] J.Sunamoto: "Synthesis and Characterization of 1,2ーDimyristoylamidoー1,αーdeoxyphosphatidylcholine as a Bounclary Lipid Model." Biochim.Biophys.Acta. 1024. 209-219 (1990)
[Publications] J.Sunamoto: "Devterium Nuclear Magnetic Resonance Studies on the Interaction of Glycophorin with 1,2ーDimyristoylamidoー1,2ーdeoxyphosphatidylcholine" Biochim.Biophys.Acta. 1024. 220-226 (1990)
[Publications] J.Sunamoto: "Effective Transfer of Membrane Proteins from Human Erythrocytes to Artifical Boundary Lipid Containing Liposomes." Chem.,Lett.1249-1252 (1990)
[Publications] M.Haruki: "Conformation change of a inoacylーtRNA and uncharged tRNA upon complex formation with polypeptide chain elongation factor Tu" FEBS Lett.263. 361-364 (1990)
[Publications] S.Kotani: "Microtubuleーassembly inhibitor protein consists of a rigid globule essential for its activity and highly mobile coils" J.Biol.Chem.265. 1286-1292 (1990)
[Publications] H.Koide: "Biosynthesis of epidermal growth factor having nonprotein amio acid residues by Eshcerichia coli" Amio acids:Chemistry,biology and medicine (eds,G,A,Rosenthal) ESCOM Science Publishers,Leiden. 193-200 (1990)
[Publications] S.Yokoyama: "Modified uridines in the first pos tions of anticodons of tRNAs and mechanisms of codon recognition" Chromatography and Modification of Nucleosides.Part B:Biological Roles and Function of Modification (eds.C.W.Gehrke and K.C.T.Kuo) Elsevier,Amsterdam. 303-306 (1990)
[Publications] T.Miyazawa: "Structures and functions of proteins and nucleic acids in protein biosynthesis" International Reviews in Physical Chemistry. 8. 125-145 (1990)
[Publications] Yoshio Hisaeda: "Preparation and Molecular Recognition Behabior of a Hexapus Azaparacyclophane" Tetrahedron Lett.18. 49-62 (1990)
[Publications] Yukito Murakami: "Hydrophobic Vitamin B_<12>.VII.RingーExpansion Reactions Catalyzed by Hydrophobic Vitamin B_<12> in Octopus Azaparacyclophane" J.Coord.Chem.21. 13-22 (1990)
[Publications] S.Kotani: "Mechanism of the interaction between microbutuleーassociated proteins and microbutules.A protein nuclear magnetic resonance analysis on the binding of synthetic peptide to tubulin" Biochemistry. (1990)
[Publications] A.Kanamori: "Deaminated neuraminic acidーrich glycoprotein(KDNーgp)of rainbow trout egg vitelline envelop" J.Biol.Chem.(1990)
[Publications] T.Kohno: "Nonprotein amio acid furanomycin,unlike isoleucine in chemical structure,is charged to isoleucine tRNA by isoleucylーtRNA synthetase and incorporated into protein" J.Biol.Chem.265. 6931-6935 (1990)
[Publications] S.Yokoyama: "NMR analyses of structures and functions of modified nucleousides in transfer ribonucleic acids." Nucleosides and Nucleotides. 9. 303-310 (1990)
[Publications] A.Nose: "Localization of Specificity Determining Sites in Cadherin Adhesion Molecules" Cell. 61. 147-155 (1990)
[Publications] A.Ikai: "Electron microscopic Demonstraction of a Common Structural Motif in Human Complement Factor C3 and Rat d1ーinhibitor 3 (murinoglobulin)" FEBS Lett.260. 291-293 (1990)
[Publications] S.Hisanaga: "Effects of Phosphorylation of the Neurofilament L Protein on Filamentous Structures" Cell Regulation.237-248 (1990)
[Publications] Yukito Murakami: "Enantioselective Catalysis by Artificial Tryptophan Synthase Formed with Functionallized Bilayer Membrane." Chemistry Letters. 15,5-17,8 (1990)
[Publications] Yukito Murakami: "Functionalized Bllayer Membranes as Artificial Tryptophan Synthase.Characterization of Catalytic Bfficiency,Substrate Specificity,and Reaction Selectivity." Bull.Chem.Soc.Jpn.63. 2339-2345 (1990)
[Publications] Yukito Murakami: "Hydrophobic Vitamin B_<12> 8.CarbonーSkeleton Rearrangement Reactions Catalyzed by Hydrophobic Vitamin B_<12> In Octopus Azaparacy clophane." Bioorg.Chem.18. 49-62 (1990)
[Publications] J.Sunamoto: "Structural Stability of Lecithin Liposomes as Improued by Adding an Artificial Boundary Lipid" Chem.Lett.2141-2144 (1990)
[Publications] A.Ochi: "Targeting Chemotherapy of Brain Tumor Using LiposomeーEncapsulated CisplatinーPart 2 PullulanーCoated Liposomes to Target Brain Tumor" D.D.S.5. 261-265 (1990)
[Publications] M.Kodama: "Thermal Characterization of a Polyethylenglycol (PEG)ーDerivative Induced Vesicle Fusion as Revealed by High Sensitivity Differential Scanning Calorimetry" Thermochimica Acta. 163. 81-88 (1990)
[Publications] Y.Noguchi: "Priming for In vitro and In vivo Anti HTLVー1 Cellular Immunity by Virus Related Protein Reconstituted into Liposome" J.Immunol.((1991))
[Publications] R.Shibata: "Indvction of in vitro and in vivo AntiーTumor Responses by Sensitization of Mice with Liposomes Containing a Crude Butanol Extract of Leukemia Cells and Transferred Intermembranously with cell surface Proteins" Int.J.Cancer. ((1991))
[Publications] M.Takeichi: "Cadherin:a Molecular Family Important in Selective CellーCell Aolhesion" Annu.Rev.Biochem.59. 237-252 (1990)

1990 Fiscal Year Annual Research Report

細胞表層の精密構造認識と機能性制御

Principal Investigator

砂本 順三 京都大学, 工学部, 教授 (80037811)

Research Products

[Publications] J.Sunamoto: "Devterium Nuclear Magnetic Resonance Studies on the Interaction of Glycophorin with 1,2ーDimyristoylamidoー1,2ーdeoxyphosphatidylcholine." Biochim.Biophys.Acta. 1024. 220-226 (1990)

[Publications] K.Akiyoshi: "Cell Specificity of Polysaccharide DerivativesonLiposomdl Surface" Chem.,Lett.473-476 (1990)

[Publications] S.Shibata: "Targeting Chemotherapy of Brain Tumor Using LiposomeーEncapsolated CisplatinーPart 1.Substances Associated with Liposomes to Target Brain Tumor" D.D.S.5. 83-87 (1990)

[Publications] J.Sunamoto: "Synthesis and Characterization of 1,2ーDimyristoylamidoー1,αーdeoxyphosphatidylcholine as a Bounclary Lipid Model." Biochim.Biophys.Acta. 1024. 209-219 (1990)

[Publications] J.Sunamoto: "Devterium Nuclear Magnetic Resonance Studies on the Interaction of Glycophorin with 1,2ーDimyristoylamidoー1,2ーdeoxyphosphatidylcholine" Biochim.Biophys.Acta. 1024. 220-226 (1990)

[Publications] J.Sunamoto: "Effective Transfer of Membrane Proteins from Human Erythrocytes to Artifical Boundary Lipid Containing Liposomes." Chem.,Lett.1249-1252 (1990)

[Publications] M.Haruki: "Conformation change of a inoacylーtRNA and uncharged tRNA upon complex formation with polypeptide chain elongation factor Tu" FEBS Lett.263. 361-364 (1990)

[Publications] S.Kotani: "Microtubuleーassembly inhibitor protein consists of a rigid globule essential for its activity and highly mobile coils" J.Biol.Chem.265. 1286-1292 (1990)

[Publications] H.Koide: "Biosynthesis of epidermal growth factor having nonprotein amio acid residues by Eshcerichia coli" Amio acids:Chemistry,biology and medicine (eds,G,A,Rosenthal) ESCOM Science Publishers,Leiden. 193-200 (1990)

[Publications] S.Yokoyama: "Modified uridines in the first pos tions of anticodons of tRNAs and mechanisms of codon recognition" Chromatography and Modification of Nucleosides.Part B:Biological Roles and Function of Modification (eds.C.W.Gehrke and K.C.T.Kuo) Elsevier,Amsterdam. 303-306 (1990)

[Publications] T.Miyazawa: "Structures and functions of proteins and nucleic acids in protein biosynthesis" International Reviews in Physical Chemistry. 8. 125-145 (1990)

[Publications] Yoshio Hisaeda: "Preparation and Molecular Recognition Behabior of a Hexapus Azaparacyclophane" Tetrahedron Lett.18. 49-62 (1990)

[Publications] Yukito Murakami: "Hydrophobic Vitamin B_<12>.VII.RingーExpansion Reactions Catalyzed by Hydrophobic Vitamin B_<12> in Octopus Azaparacyclophane" J.Coord.Chem.21. 13-22 (1990)

[Publications] S.Kotani: "Mechanism of the interaction between microbutuleーassociated proteins and microbutules.A protein nuclear magnetic resonance analysis on the binding of synthetic peptide to tubulin" Biochemistry. (1990)

[Publications] A.Kanamori: "Deaminated neuraminic acidーrich glycoprotein(KDNーgp)of rainbow trout egg vitelline envelop" J.Biol.Chem.(1990)

[Publications] T.Kohno: "Nonprotein amio acid furanomycin,unlike isoleucine in chemical structure,is charged to isoleucine tRNA by isoleucylーtRNA synthetase and incorporated into protein" J.Biol.Chem.265. 6931-6935 (1990)

[Publications] S.Yokoyama: "NMR analyses of structures and functions of modified nucleousides in transfer ribonucleic acids." Nucleosides and Nucleotides. 9. 303-310 (1990)

[Publications] A.Nose: "Localization of Specificity Determining Sites in Cadherin Adhesion Molecules" Cell. 61. 147-155 (1990)

[Publications] A.Ikai: "Electron microscopic Demonstraction of a Common Structural Motif in Human Complement Factor C3 and Rat d1ーinhibitor 3 (murinoglobulin)" FEBS Lett.260. 291-293 (1990)

[Publications] S.Hisanaga: "Effects of Phosphorylation of the Neurofilament L Protein on Filamentous Structures" Cell Regulation.237-248 (1990)

[Publications] Yukito Murakami: "Enantioselective Catalysis by Artificial Tryptophan Synthase Formed with Functionallized Bilayer Membrane." Chemistry Letters. 15,5-17,8 (1990)

[Publications] Yukito Murakami: "Functionalized Bllayer Membranes as Artificial Tryptophan Synthase.Characterization of Catalytic Bfficiency,Substrate Specificity,and Reaction Selectivity." Bull.Chem.Soc.Jpn.63. 2339-2345 (1990)

[Publications] Yukito Murakami: "Hydrophobic Vitamin B_<12> 8.CarbonーSkeleton Rearrangement Reactions Catalyzed by Hydrophobic Vitamin B_<12> In Octopus Azaparacy clophane." Bioorg.Chem.18. 49-62 (1990)

[Publications] J.Sunamoto: "Structural Stability of Lecithin Liposomes as Improued by Adding an Artificial Boundary Lipid" Chem.Lett.2141-2144 (1990)

[Publications] A.Ochi: "Targeting Chemotherapy of Brain Tumor Using LiposomeーEncapsulated CisplatinーPart 2 PullulanーCoated Liposomes to Target Brain Tumor" D.D.S.5. 261-265 (1990)

[Publications] M.Kodama: "Thermal Characterization of a Polyethylenglycol (PEG)ーDerivative Induced Vesicle Fusion as Revealed by High Sensitivity Differential Scanning Calorimetry" Thermochimica Acta. 163. 81-88 (1990)

[Publications] Y.Noguchi: "Priming for In vitro and In vivo Anti HTLVー1 Cellular Immunity by Virus Related Protein Reconstituted into Liposome" J.Immunol.((1991))

[Publications] R.Shibata: "Indvction of in vitro and in vivo AntiーTumor Responses by Sensitization of Mice with Liposomes Containing a Crude Butanol Extract of Leukemia Cells and Transferred Intermembranously with cell surface Proteins" Int.J.Cancer. ((1991))

[Publications] M.Takeichi: "Cadherin:a Molecular Family Important in Selective CellーCell Aolhesion" Annu.Rev.Biochem.59. 237-252 (1990)

砂本順三京都大学, 工学部, 教授 (80037811)